P38 MAPK Signaling Mediates Retinoic Acid-Induced CD103 Expression in Human Dendritic Cells.
In this study, we analyzed the cell type specificity and the molecular mechanisms involved in RA-induced CD103 expression. We show that RA treatment caused a significant upregulation of CD103 in differentiated monocyte-derived DCs and blood DCs, but not in differentiated monocyte-derived macrophages or T cells. DC treatment with an RARα agonist lead to a similar increase in CD103 expression as RA treatment, while RARA gene silencing with siRNA blocked RA-induced upregulation of CD103, pointing to a major role of RARα in the regulation of CD103 expression. To elucidate RA-induced signaling downstream of RAR&alph...
Source: Immunology - August 1, 2020 Category: Allergy & Immunology Authors: Roe MM, Hashimi M, Swain S, Woo KM, Bimczok D Tags: Immunology Source Type: research

The role of O-GlcNAcylation in immunity against infections.
Abstract Mounting an effective immune response is crucial for the host to protect itself against invading pathogens. It is now well appreciated that reprogramming of core metabolic pathways in immune cells is a key requirement for their activation and function during infections. The role of several ancillary metabolic pathways in shaping immune cell function is less well understood. One such pathway, for which interest has recently been growing, is the hexosamine biosynthesis pathway (HBP) that generates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the donor substrate for a specific form of glycosylation ...
Source: Immunology - August 1, 2020 Category: Allergy & Immunology Authors: Quik M, Hokke CH, Everts B Tags: Immunology Source Type: research

Erratum.
Authors: PMID: 32686182 [PubMed - in process] (Source: Immunology)
Source: Immunology - July 22, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

T cells and cytokines in inflamed psoriatic skin. Who's in charge?
Abstract Inflammation in psoriasis is driven through the IL-23/IL-17 pathway. Monoclonal antibodies targeting cytokines in the pathway have proven highly effective and are widely used in clinical practice. There is still much to learn, however, about how these pathogenic responses are controlled, particularly with respect to the highly immunologically active molecules produced by the inflamed skin tissue itself. These tissue-derived molecules, which include IL-33, play important roles in modulating chronic inflammation that we are only beginning to understand. Here we highlight new research indicating a role for I...
Source: Immunology - July 22, 2020 Category: Allergy & Immunology Authors: Milling S, Siebert S Tags: Immunology Source Type: research

Corrigendum.
Authors: PMID: 32686184 [PubMed - in process] (Source: Immunology)
Source: Immunology - July 22, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

Viruses and asthma: the role of common respiratory viruses in asthma and its potential meaning for SARS-CoV-2.
Abstract Viral infections and atopic diseases are closely related and contribute to each other. The physiological deficiencies and immune mechanisms that underlie atopic diseases can result in a suboptimal defense against multiple viruses and promote a suitable environment for their proliferation and dissemination. Viral infections, on the other hand, can induce per se several immunological mechanisms involved in allergic inflammation capable to promote the initiation or exacerbation of atopic diseases such as atopic asthma. In a world that is affected more and more by factors that significantly impact the prevale...
Source: Immunology - July 20, 2020 Category: Allergy & Immunology Authors: Novak N, Cabanillas B Tags: Immunology Source Type: research

Quantifying immunoregulation by autoantigen-specific T-regulatory type 1 cells in mice with simultaneous hepatic and extra-hepatic autoimmune disorders.
Abstract Nanoparticles displaying autoimmune disease-relevant peptide-major histocompatibility complex class II molecules (pMHCII-NPs) trigger cognate T-regulatory type 1 (Tr1)-cell formation and expansion, capable of reversing organ-specific autoimmune responses. These pMHCII-NPs that display epitopes from mitochondrial protein can blunt the progression of both autoimmune hepatitis (AIH) and experimental autoimmune encephalomyelitis (EAE) in mice carrying either disease. However, with comorbid mice having both diseases, these pMHCII-NPs selectively treat AIH. In contrast, pMHCII-NPs displaying central nervous sys...
Source: Immunology - July 20, 2020 Category: Allergy & Immunology Authors: Jamaleddine H, Santamaria P, Khadra A Tags: Immunology Source Type: research

Targeting Metabolism to Reverse T-cell Exhaustion in Chronic Viral Infections.
Abstract CD8 T-cells are an essential component of immune response to viral infections; however, in certain instances, such as chronic infections, they can reach an exhausted state, where T-cells loose glycolytic activity together with cytotoxic capacity. Recent research has indicated that correcting this dysfunctional metabolic state could be key to reversing exhaustion and allowing for proper clearance of chronic viral infections. Here, we review current knowledge about T-cell exhaustion during infection and discuss strategies targeting metabolism that hold promise for its reversal. PMID: 32681647 [PubMed -...
Source: Immunology - July 18, 2020 Category: Allergy & Immunology Authors: Sears JD, Waldron KJ, Wei J, Chang CH Tags: Immunology Source Type: research

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data.
Abstract According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in A...
Source: Immunology - July 18, 2020 Category: Allergy & Immunology Authors: Toufiq M, Roelands J, Alfaki M, Ahamed Kabeer B, Saadaoui M, Prasath Lakshmanan A, Kumar Bangarusamy D, Murugesan S, Bedognetti D, Hendrickx W, Al Khodor S, Terranegra A, Rinchai D, Chaussabel D, Garand M Tags: Immunology Source Type: research

The battle for iron in enteric infections.
st JN Abstract Iron is an essential element for almost all living organisms, which can also be extremely toxic in high concentrations. All organisms must therefore employ homeostatic mechanisms to finely regulate iron uptake, usage and storage in the face of dynamic environmental conditions. The critical step in mammalian systemic iron homeostasis is the fine regulation of dietary iron absorption. However, since the gastrointestinal system is also home to>1014 bacteria, all of which engage in their own programs of iron homeostasis, the gut represents an anatomical location where the inter-kingdom fight for iron...
Source: Immunology - July 8, 2020 Category: Allergy & Immunology Authors: Sousa Gerós A, Simmons A, Drakesmith H, Aulicino A, Frost JN Tags: Immunology Source Type: research

MHC class I transactivator NLRC5 in host immunity, cancer and beyond.
Abstract The presentation of antigenic peptides by major histocompatibility complex (MHC) class I and class II molecules are crucial for activation of the adaptive immune system. The nucleotide-binding domain and leucine-rich repeat receptor family member, CIITA and NLRC5 functions as the major transcriptional activator of MHC class II and class I gene expression, respectively. Since the identification of NLRC5 as the master regulator of MHC class I and class I related genes, there has been major advances in understanding the function of NLRC5 in infectious diseases and cancer. Here, we discuss the biological sign...
Source: Immunology - July 7, 2020 Category: Allergy & Immunology Authors: Cho SX, Vijayan S, Yoo JS, Watanabe T, Ouda R, Ning A, Kobayashi KS Tags: Immunology Source Type: research

Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin-derived mutant epitopes.
kian G, Manoutcharian K Abstract Immune tolerance is the main challenge in the field of cancer vaccines, therefore, modified peptide sequences or naturally occurring mutated versions of cancer-related wild-type (WT) antigens represent a promising pathway. However, low immunogenicity of mutation-induced neoantigens and, particularly, their incapacity to activate CD8+ T cells are generating doubts on the success of neoantigen-based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called Variable Epitope Libraries (VELs). We used 3 regions of surviv...
Source: Immunology - July 3, 2020 Category: Allergy & Immunology Authors: Domínguez-Romero AN, Martínez-Cortés F, Munguía ME, Odales J, Gevorkian G, Manoutcharian K Tags: Immunology Source Type: research

Schistosome and intestinal helminth modulation of Macrophage Immunometabolism.
Abstract Macrophages are fundamental to sustain physiological equilibrium and to regulate the pathogenesis of parasitic and metabolic processes. The functional heterogeneity and immune responses of macrophages are shaped by cellular metabolism in response to the host's intrinsic factors, environmental cues and other stimuli during disease. Parasite infections induce a complex cascade of cytokines and metabolites that profoundly remodel the metabolic status of macrophages. In particular, helminths polarize macrophages to a M2 state and induce a metabolic shift towards a reliance on oxidative phosphorylation, lipid ...
Source: Immunology - July 2, 2020 Category: Allergy & Immunology Authors: Cortes-Selva D, Fairfax K Tags: Immunology Source Type: research

A behind the scenes tour of the IEDB curation process: an optimized process empirically integrating automation and human curation efforts.
Abstract The Immune Epitope Database and Analysis Resource (IEDB) provides the scientific community open access to epitope data, as well as epitope prediction and analysis tools. The IEDB houses the most extensive collection of experimentally validated B cell and T cell epitope data, sourced primarily from published literature by expert curation. The data procurement requires systematic identification, categorization, curation, and quality-checking processes. Here we provide insights into these processes, with particular focus on the dividends they have paid in terms of attaining project milestones, as well as how...
Source: Immunology - July 2, 2020 Category: Allergy & Immunology Authors: Salimi N, Edwards L, Foos G, Greenbaum JA, Martini S, Reardon B, Shackelford D, Vita R, Zalman L, Peters B, Sette A Tags: Immunology Source Type: research

Role of myeloid cells in the regulation of ILC2-mediated allergic inflammation.
Abstract Group 2 innate lymphoid cells (ILC2s) are an important component of the innate immune system that execute important effector functions at barrier surfaces, such as lung and skin. Like Th2 cells, ILC2s are able to release high amounts of type 2 cytokines that are essential in inducing allergic inflammation and eliminating helminth infections. The past few years have contributed to our better understanding of the interactions between ILC2s and other cells of immune system via soluble factors or in a cell-cell contact manner. Myeloid cells, including mononuclear leukocytes and polymorphonuclear leukocytes, a...
Source: Immunology - July 1, 2020 Category: Allergy & Immunology Authors: Lei A, He Y, Yang Q, Li X, Li R Tags: Immunology Source Type: research

Gasdermin D-independent release of interleukin-1b by living macrophages in response to mycoplasmal lipoproteins and lipopeptides.
Abstract Interleukin-1b (IL-1b) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1b by caspase-1 which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell death-mediated release of IL-1b. Living cells can also release IL-1b via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and...
Source: Immunology - June 26, 2020 Category: Allergy & Immunology Authors: Saeki A, Tsuchiya K, Suda T, Into T, Hasebe A, Suzuki T, Shibata KI Tags: Immunology Source Type: research

Complement activation by human IgG antibodies to galactose-alpha-1,3-galactose.
iel S Abstract Some human antibodies may paradoxically inhibit complement activation on bacteria and enhance pathogen survival in humans. This property was also claimed for IgG antibodies reacting with terminal Galα3Gal (IgG anti-αGal), a naturally occurring and abundant antibody in human plasma that targets numerous different pathogens. To reinvestigate these effects, we utilised IgG anti-αGal affinity isolated from a pool of normal human IgG and human hypogammaglobulinemia serum as a complement source. Flow cytometry was performed to examine antibody binding and complement deposition on pig ery...
Source: Immunology - June 24, 2020 Category: Allergy & Immunology Authors: Bernth Jensen JM, Laursen NS, Kjeldsen Jensen R, Andersen GR, Jensenius JC, Skov Sørensen UB, Thiel S Tags: Immunology Source Type: research

Characterising the original anti-C5 function-blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5.
Abstract The implication of complement in multiple diseases over the last twenty years has fuelled interest in developing anti-complement drugs. To date, the focus has been on C5; blocking cleavage of C5 prevents formation of two pro-inflammatory activities, C5a anaphylatoxin and membrane attack complex. The concept of C5 blockade to inhibit inflammation dates back thirty years to the description of BB5.1, an anti-C5 blocking monoclonal antibody raised in C5-deficient mice. This antibody proved an invaluable tool to demonstrate complement involvement in mouse disease models and catalysed enthusiasm for anti-comple...
Source: Immunology - June 17, 2020 Category: Allergy & Immunology Authors: Zelek WM, Menzies GE, Brancale A, Stockinger B, Morgan BP Tags: Immunology Source Type: research

The UK Veterinary Immunological Toolbox Website: promoting vaccine research by facilitating communication and removing reagent barriers.
Abstract Using the best animal models to study immune responses against specific pathogens or vaccines can dramatically accelerate our understanding. Veterinary species are well studied, particularly livestock, to reduce their disease burden. They have also proven to be powerful models, especially for zoonotic pathogens and novel vaccination strategies. A prerequisite for any model selection is having the right quality and range of species-specific immunological reagents. To help promote the widest possible use of veterinary species, an open access website (https://www.immunologicaltoolbox.co.uk) has been created ...
Source: Immunology - June 16, 2020 Category: Allergy & Immunology Authors: Mwangi W, Maccari G, Hope JC, Entrican G, Hammond JA Tags: Immunology Source Type: research

Landscape of Variable Domain of Heavy-chain-only Antibody Repertoire from Alpaca.
Abstract Heavy-chain-only antibodies (HCAbs), which are devoid of light chains, have been found naturally occurring in various species including camelids and cartilaginous fish. Due to their high thermostability, refoldability, and capacity for cell permeation, the variable regions of heavy chain of HCAbs (VHHs) have been widely used in diagnosis, bio-image, food safety, and therapeutics. Most immunogenetic and functional studies of HCAbs are based on case studies or a limited number of low throughput sequencing data. A complete picture derived from more abundant high-throughput sequencing (HTS) data can help us g...
Source: Immunology - June 7, 2020 Category: Allergy & Immunology Authors: Tu Z, Huang X, Fu J, Hu N, Zheng W, Li Y, Zhang Y Tags: Immunology Source Type: research

Immunological fortification at our barrier organs: Protecting us as we age.
Abstract Our barrier surfaces are fundamental in protecting us from the outside world and segregating key biological processes. The immunological fortifications found at these sites therefore possess many distinct qualities, which are discussed in Immunology's series of reviews on Barrier Immunity. Together these reviews showcase novel biological processes identified through the use of state-of-the-art technologies, and specifically highlight how these change throughout our lives. PMID: 32400027 [PubMed - in process] (Source: Immunology)
Source: Immunology - May 15, 2020 Category: Allergy & Immunology Authors: Harker JA, Pallett LJ Tags: Immunology Source Type: research

Tbet promotes CXCR6 expression in immature NK cells and NK cell egress from the bone marrow.
Abstract Tbet-deficient mice have reduced NK cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be due to defective migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet-deficient Tbx21-/- animals occurs because of a migration defect and identify a module of genes, co-ordinated by Tbet, which affects the localisation of NK cells in the bone marrow. Cxcr6 is approximately 125-fold underexpressed in Tbx21-/- , compared to wild-type, immature NK cells. I...
Source: Immunology - May 8, 2020 Category: Allergy & Immunology Authors: Cuff AO, Perchet T, Dertschnig S, Golub R, Male V Tags: Immunology Source Type: research

Guide to Immunopharmacology: a database to boost immunology education, research and therapy.
Abstract In the era of big data, the establishment of a free database, containing all the immune drug targets and associated cell types, is of great value. To this aim, the Guide to Immunopharmacology has been created in a joint effort between the International Union of Basic and Clinical Pharmacology (IUPHAR) and the International Union of Immunological Societies (IUIS). Here we highlight the structure and content of the database, which includes up-to-date quantitative information on the fundamental science underlying each immune target. A set of practical examples and tools for data mining are summarized to supp...
Source: Immunology - April 18, 2020 Category: Allergy & Immunology Authors: Milling S, Spedding M, Maffia P Tags: Immunology Source Type: research

Understanding the mechanisms that facilitate specificity, not redundancy, of chemokine mediated leukocyte recruitment.
Abstract Chemokines (chemotactic cytokines) and their receptors are critical to recruitment and positioning of cells during development and the immune response. The chemokine system has long been described as redundant for a number of reasons, where multiple chemokine ligands can bind to multiple receptors and vice versa. This apparent redundancy has been thought to be a major reason for the failure of drugs targeting chemokines during inflammatory disease. We are now beginning to understand that chemokine biology is in fact based around a high degree of specificity, where each chemokine and receptor plays a parti...
Source: Immunology - April 13, 2020 Category: Allergy & Immunology Authors: Dyer DP Tags: Immunology Source Type: research

GSK3 promotes Th17 differentiation by promoting IL-9 production.
Abstract T helper (Th)17 cells have become recognized as important contributors to the deleterious effects of several neurological and psychiatric diseases. Clarifying mechanisms that control the production of Th17 cells may therefore provide new strategies for developing novel interventions in a broad spectrum of disorders. Th17 cell differentiation is promoted by glycogen synthase kinase-3 (GSK3), but the mechanisms for this are only beginning to be understood. Using T cell-selective depletion of GSK3β and multiple selective pharmacological GSK3 inhibitors, we found that GSK3 inhibition decreased C-C motif ...
Source: Immunology - April 11, 2020 Category: Allergy & Immunology Authors: Han D, Medina-Rodriguez EM, Lowell J, Beurel E Tags: Immunology Source Type: research

The Role of B Cells in the Immunopathogenesis of Multiple Sclerosis.
Abstract Over the last years, there has been an ongoing debate on how B cells contribute to the pathogenesis of multiple sclerosis (MS). The success of B cell targeting therapies in MS highlighted the role of B cells particularly the antibody-independent functions of these cells such as antigen presentation to T cells and modulation of the function of T cells and myeloid cells by secreting pathogenic and/or protective cytokines in the central nervous system (CNS). Here, we discuss the role of different antibody-dependent and antibody-independent functions of B cells in MS disease activity and progression proposing...
Source: Immunology - April 6, 2020 Category: Allergy & Immunology Authors: Gharibi T, Babaloo Z, Hosseini A, Marofi F, Ebrahimi-Kalan A, Jahandideh S, Baradaran B Tags: Immunology Source Type: research

Ageing dangerously; homing of senescent CD8 T cells in cutaneous Leishmaniasis.
Abstract Both CD8+ T cells and NK cells contribute to the immune response against the protozoan Leishmania parasite. Both are able to generate IFN-γ and both display cytotoxic features. These features may enable them to not only contribute to parasite clearance but also to cause immune-mediated pathology. This pathology is evident, for example, in the Leismania-induced skin lesions found in patients with cutaneous leismaniasis (CL). Here we highlight new data demonstrating that CD8+ T cells and NK cells in CL display a highly cytotoxic senescent phenotype, and that the senescent T cells play a major role in ...
Source: Immunology - March 19, 2020 Category: Allergy & Immunology Authors: Milling S Tags: Immunology Source Type: research

A role for cell-autocrine interleukin-2 in regulatory T cell homeostasis.
Abstract Activated T cells make both interleukin-2 (IL2) and its high-affinity receptor component CD25. Regulatory CD4 T cells (Treg cells) do not make IL2, and the IL2-CD25 circuit is considered a paracrine circuit crucial in their generation and maintenance. Yet, all T cells are capable of making IL2 at some stage during differentiation, making a cell-intrinsic autocrine circuit additionally possible. When we re-visited experiments with mixed bone marrow chimeras using a wide range of ratios of WT and IL2-/- genotype progenitors, we found that, as expected, thymic Treg cells were almost equivalent between WT and...
Source: Immunology - March 18, 2020 Category: Allergy & Immunology Authors: Chawla AS, Khalsa JK, Dhar A, Gupta S, Umar D, Arimbasseri GA, Bal V, George A, Rath S Tags: Immunology Source Type: research

Immunological roles of intestinal mesenchymal cells.
Abstract The intestine is continuously exposed to an enormous variety and quantity of antigens and innate immune stimuli derived from both pathogens and harmless materials, such as food and commensal bacteria. Accordingly, the intestinal immune system is uniquely adapted to ensure appropriate responses to the different kinds of challenge; maintaining tolerance to harmless antigens in the steady state, whilst remaining poised to deal with potential pathogens. To accomplish this, leukocytes of the intestinal immune system have to adapt to a constantly changing environment and interact with many different non-leukocy...
Source: Immunology - March 17, 2020 Category: Allergy & Immunology Authors: Thomson CA, Nibbs RJ, McCoy KD, Mowat AM Tags: Immunology Source Type: research

The immunological network in the developing human skin.
Abstract Establishment of a well-functioning immune network in skin is crucial for its barrier function. This begins in utero alongside the structural differentiation and maturation of skin, and continues to expand and diversify across the human lifespan. The microenvironment of the developing human skin supports immune cell differentiation and has an overall anti-inflammatory profile. Immunologically inert and skewed immune populations found in developing human skin promote wound healing, and as such may play a crucial role in the structural changes occurring during skin development. PMID: 32173857 [PubMed -...
Source: Immunology - March 16, 2020 Category: Allergy & Immunology Authors: Botting RA, Haniffa M Tags: Immunology Source Type: research

The Liver as an Immunological Barrier Redefined by Single Cell Analysis.
Abstract The liver is a front-line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the blood-stream, especially from the gut. Our largest internal organ maintains this immune barrier in the face of constant exposure to external but harmless antigens through a highly specialised network of liver-adapted immune cells. Mapping the immune resident compartment in the liver has been challenging because it requires multimodal single-cell deep phenotyping approaches of often rare cell populations in difficult to access samples. We can now measure the...
Source: Immunology - March 16, 2020 Category: Allergy & Immunology Authors: Stamataki Z, Swadling L Tags: Immunology Source Type: research

Regulatory T cells in Helminth Infection: Induction, Function and Therapeutic Potential.
Abstract Helminth parasites infect an alarmingly large proportion of the world's population, primarily within tropical regions, and their ability to down-modulate host immunity is key to their persistence. Helminths have developed multiple mechanisms that induce a state of hyporesponsiveness or immune suppression within the host; of particular interest are mechanisms that drive the induction of regulatory T cells (Tregs). Helminths actively induce Tregs either directly by secreting factors, such as the TGF-β mimic Hp-TGM, or indirectly by interacting with bystander cell types such as dendritic cells and macro...
Source: Immunology - March 10, 2020 Category: Allergy & Immunology Authors: White MPJ, McManus CM, Maizels RM Tags: Immunology Source Type: research

Insufficient CD100 shedding contributes to suppression of CD8+ T cell activity in non-small cell lung cancer.
Abstract CD100 is an immune semaphorin constitutively expressed on T cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8+ T cells were analysed in NSCLC patients. The ability to i...
Source: Immunology - March 9, 2020 Category: Allergy & Immunology Authors: Wang HM, Zhang XH, Ye LQ, Zhang K, Yang NN, Geng S, Chen J, Zhao SX, Yang KL, Fan FF Tags: Immunology Source Type: research

T cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumor burden in multiple murine syngeneic models of solid cancer.
Abstract Adoptive transfer of T cells is a promising therapy for many cancers. To enhance tumor recognition by T cells, chimeric antigen receptors (CAR) consisting of signaling domains fused to receptors that recognize tumor-associated antigens can be expressed in T cells. While CAR T cells have shown clinical success for treating hematopoietic malignancies, using CAR T cells to treat solid tumors remains a challenge. We developed a chimeric PD1 (chPD1) receptor that recognizes the ligands for the PD1 receptor which are expressed on many types of solid cancer. To determine if this novel CAR could target a wide var...
Source: Immunology - March 7, 2020 Category: Allergy & Immunology Authors: Parriott G, Deal K, Crean S, Richardson E, Nylen E, Barber A Tags: Immunology Source Type: research

NF- κB-inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T cell repertoire.
NF-κB-inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T cell repertoire. Immunology. 2020 Mar 07;: Authors: Eshima K, Misawa K, Ohashi C, Noma H, Iwabuchi K Abstract NF-κB-inducing kinase (NIK) is known to be a critical regulator of multiple aspects of the immune response. Although the role of NIK in the development of medullary thymic epithelial cells (mTECs) has been well documented, the impact of NIK on the differentiation and function of cortical thymic epithelial cells (cTECs) remains ambiguous. To investigat...
Source: Immunology - March 7, 2020 Category: Allergy & Immunology Authors: Eshima K, Misawa K, Ohashi C, Noma H, Iwabuchi K Tags: Immunology Source Type: research

T cells producing multiple combinations of IFN γ, TNF and IL10 are associated with mild forms of dengue infection.
T cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection. Immunology. 2020 Mar 03;: Authors: Gonçalves Pereira MH, Figueiredo MM, Queiroz CP, Magalhães TVB, Mafra A, Diniz LMO, da Costa ÚL, Gollob KJ, do Valle Antonelli LR, da Costa Santiago H Abstract Multifunctional IL10+ Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4+ and CD8+ T cells which expressed IF...
Source: Immunology - March 3, 2020 Category: Allergy & Immunology Authors: Gonçalves Pereira MH, Figueiredo MM, Queiroz CP, Magalhães TVB, Mafra A, Diniz LMO, da Costa ÚL, Gollob KJ, do Valle Antonelli LR, da Costa Santiago H Tags: Immunology Source Type: research

Recovery training or over-training? The contribution of TLR10 to monocyte fitness.
Abstract The concept of trained immunity refers to remodelling of the monocyte and macrophage metabolic and epigenetic landscape, conferring an amplified inflammatory response upon secondary stimulation. This effect is typically modelled in vitro by stimulating monocytes with either Bacillus Calmette Guerin (BCG) or β-Glucan for 24 hr, before subsequent stimulation with LPS or Pam-3-Cys (P3C) as a secondary stimulus 6 days later. Here, we focus on a recent paper which interrogated the role of the anti-inflammatory TLR, TLR10, on trained immunity. Using both an in vitro model of trained immunity, and...
Source: Immunology - February 13, 2020 Category: Allergy & Immunology Authors: Rodgers L, Milling S Tags: Immunology Source Type: research

V(D)J Recombination, Somatic Hypermutation and Class Switch Recombination of Immunoglobulins: Mechanism and Regulation.
Abstract Immunoglobulins (Ig) emerged from B lymphocytes, capable of recognizing almost all kinds of antigens owing to the extreme diversity of their antigen binding portions known as variable (V) regions, plays an important role in immune response. The exons encoding the V regions are known as V (variable), D (diversity), J (joining) genes. V, D, J segments exist as multiple copy arrays on the chromosome. The recombination of V(D)J gene are the key mechanism to produce antibody diversity. The recombinational process including randomly choosing a pair of V, D, J segments, introducing double strand-breaks (DSBs) ad...
Source: Immunology - February 7, 2020 Category: Allergy & Immunology Authors: Chi X, Li Y, Qiu X Tags: Immunology Source Type: research

DNA methylation-mediated Siglec-7 regulation in natural killer cells via two 5' promoter CpG sites.
In this study, we aimed to investigate how cell surface Siglec-7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK-92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5' Siglec-7 promoter became noticeably hypomethylated, and Siglec-7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec-7 expression. Additionally, by using histone deacety...
Source: Immunology - February 6, 2020 Category: Allergy & Immunology Authors: Huang HT, Su SC, Chiou TJ, Lin YH, Shih YC, Wu YX, Fan TH, Twu YC Tags: Immunology Source Type: research

The IUPHAR Guide to Immunopharmacology: Connecting Immunology and Pharmacology.
Abstract Given the critical role that the immune system plays in a multitude of diseases, having a clear understanding of the pharmacology of the immune system is crucial to new drug discovery and development. Here we describe the IUPHAR Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb), which connects expert-curated pharmacology with key immunological concepts and aims to put pharmacological data into the hands of immunologists. In the pursuit of new therapeutics, pharmacological databases are a vital resource to researchers through providing accurate information on the fundamental science underlying drug action. This ext...
Source: Immunology - February 5, 2020 Category: Allergy & Immunology Authors: Harding SD, Faccenda E, Southan C, Pawson AJ, Maffia P, Alexander SPH, Davenport AP, Fabbro D, Levi-Schaffer F, Spedding M, Davies JA Tags: Immunology Source Type: research

Control of regulatory T-cell differentiation and function by T-cell receptor signalling and Foxp3 transcription factor complexes.
Abstract The transcription factor Foxp3 controls the differentiation and function of regulatory T-cells (Treg). Studies in the past decades identified numerous Foxp3-interacting protein partners. However, it is still not clear how Foxp3 produces the Treg-type transcriptomic landscape through cooperating with its partners. Here I show the current understanding of how Foxp3 transcription factor complexes regulate the differentiation, maintenance, and functional maturation of Treg. Importantly, T-cell receptor (TCR) signalling plays central roles in Treg differentiation and Foxp3-mediated gene regulation. Thus, diffe...
Source: Immunology - February 5, 2020 Category: Allergy & Immunology Authors: Ono M Tags: Immunology Source Type: research

Corrigendum.
Authors: PMID: 31926026 [PubMed - in process] (Source: Immunology)
Source: Immunology - January 12, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

Should we be more cre-tical? A cautionary tale of recombination.
Abstract The cre-loxP system has been revolutionary in the field of immunology. The technology enables genetic deletion in mice with unprecedented precision. It is therefore now widely used to investigate gene functions in animal models of disease, and in fundamental studies of the immune response. This widespread adoption of cre-loxP technology has allowed a thorough investigation of its strengths and weaknesses. Here we highlight an important paper which not only describes potential problems with the commonly-used screening procedures used when identifying offspring of the correct genotype, but also describes ho...
Source: Immunology - January 12, 2020 Category: Allergy & Immunology Authors: Andrusaite A, Milling S Tags: Immunology Source Type: research

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8+ T cells in human cutaneous leishmaniasis.
Abstract Cytotoxic activity mediated by CD8+ T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of NK cells phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than...
Source: Immunology - January 10, 2020 Category: Allergy & Immunology Authors: Covre LP, Devine O, Garcia de Moura R, Vukmanovic-Stejic M, Dietze R, Rodrigues RR, Guedes HLM, Lubiana Zanotti R, Falqueto A, Akbar AN, Gomes DCO Tags: Immunology Source Type: research

The Blockade of CC Chemokine Receptor Type 1 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in a Rat Model of Neuropathic Pain.
Abstract A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the scia...
Source: Immunology - January 9, 2020 Category: Allergy & Immunology Authors: Pawlik K, Piotrowska A, Kwiatkowski K, Ciapała K, Popiolek-Barczyk K, Makuch W, Mika J Tags: Immunology Source Type: research

CD8 α- conventional dendritic cells control Vβ T cell immunity in response to Staphylococcus aureus infection in mice.
In this study, we examined the function of spleen DC subsets in the activation of immunity against S. aureus infection. C57BL/6 mice were infected intravenously with S. aureus and DC and T cell activation were analyzed in vivo. We found that the spleen CD8α- cDCs phagocytosed S. aureus more efficiently than type-1 conventional DCs (cDC1s) did. Moreover, the CD8α- cDCs contributed to the production of pro-inflammatory cytokines in response to S. aureus infection, while the cDC1s did not. In addition, infection with S. aureus promoted an increase in the number of Vβ T cells. The CD4+ and CD8+ Vβ T cells...
Source: Immunology - January 7, 2020 Category: Allergy & Immunology Authors: Zhang W, Xu L, Zhang X, Xu J, Jin JO Tags: Immunology Source Type: research

SLAMF9 is found on select subsets of antigen-presenting cells and promotes resistance to Salmonella infection.
Abstract SLAMF9 is an orphan receptor of the CD2/SLAM family of leucocyte surface proteins. Examination of SLAMF9 expression and function indicates that SLAMF9 promotes inflammation by specialized subsets of antigen presenting cells. Within healthy liver and circulating mouse PBMCs, SLAMF9 is expressed on CD11b+, Ly6C-, CD11clow , F4/80low , MHC-II+, CX3 CR1+ mononuclear phagocytes as well as plasmacytoid dendritic cells. In addition, SLAMF9 can be found on peritoneal B1 cells and small (F4/80low ), but not large (F4/80high ), peritoneal macrophages. Upon systemic challenge with Salmonella enterica Typhimurium, Sl...
Source: Immunology - December 27, 2019 Category: Allergy & Immunology Authors: Wilson TJ, Clare S, Mikulin J, Johnson CM, Harcourt K, Lyons PA, Dougan G, Smith KGC Tags: Immunology Source Type: research

Identification of a HLA-A*24:02-restricted alpha-fetoprotein signal peptide derived antigen and its specific T cell receptor for T cell immunotherapy.
Abstract Hepatocellular carcinoma (HCC) is the most common type of liver cancer with limited treatments. Asia has the highest HCC incidence rates; China accounts for over 50% of all HCC cases worldwide. T-cell receptor (TCR)-engineered T cell immunotherapies specific for HLA-A*02:01 restricted alpha-fetoprotein (AFP) peptide have shown encouraging results in clinics. HLA-A*24:02 is more common than HLA-A*02:01 in Asian countries including China. Here we identified a novel HLA-A*24:02 restricted peptide KWVESIFLIF (AFP2-11 ) located in AFP signal peptide domain by mass spectrometric analysis of HLA bound peptides f...
Source: Immunology - December 17, 2019 Category: Allergy & Immunology Authors: Li Z, Gong H, Liu Q, Wu W, Cheng J, Mei Y, Chen Y, Zheng H, Yu X, Zhong S, Li Y Tags: Immunology Source Type: research

Circadian rhythms in adaptive immunity.
Abstract The circadian clock provides organisms with the ability to track time of day, allowing them to predict and respond to cyclical changes in the external environment. In mammals this clock consists of multiple auto-regulatory feedback loops generated by a network of circadian clock proteins. This network provides the fundamental basis for rhythms in behaviour and physiology. This clockwork manchinery exists in most cells, including those of the immune system. In recent years evidence has emerged highlighting the important role of molecular clocks in dictating the response of immune pathways. While initial wo...
Source: Immunology - December 14, 2019 Category: Allergy & Immunology Authors: Downton P, Early JO, Gibbs JE Tags: Immunology Source Type: research

Circadian rhythms in innate immunity and stress responses.
Abstract Circadian clocks are a common feature of life on our planet, allowing physiology and behaviour to be adapted to recurrent environmental fluctuation. There is now compelling evidence that disturbance of circadian coherence can severely undermine mental and physical health, as well as exacerbate pre-existing pathology. Common molecular design principles underpin the generation of cellular circadian rhythms across the kingdoms, and in animals the genetic components are extremely well conserved. In mammals, the circadian timing mechanism is present in most cell types and establishes local cycles of gene expre...
Source: Immunology - December 10, 2019 Category: Allergy & Immunology Authors: Baxter M, Ray DW Tags: Immunology Source Type: research