Genetic Screening for Novel Regulators of Immune Checkpoint Molecules.
Abstract Inhibitory and stimulatory immune checkpoint molecules play important roles in regulating immune responses. An increasing number of these immune regulators are currently being evaluated as targets in putative anti-cancer therapies. Recently, sophisticated genetic screens have been performed to increase our understanding of immune checkpoint pathways and their immunomodulatory regulators. Here, we summarize novel insights obtained by these screens and discuss new directions to advance possible strategies to treat malignancies. PMID: 32605801 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: Arens R, Scheeren FA Tags: Trends Immunol Source Type: research

Cardiac Mast Cells: Underappreciated Immune Cells in Cardiovascular Homeostasis and Disease.
Abstract Mast cells are multifarious immune cells with complex roles in tissue homeostasis and disease. They produce a plethora of mediators that play roles in inflammation, angiogenesis, lymphangiogenesis, and tissue remodeling. Recent insights into the heterogeneity of cardiac mast cell (CMC) subpopulations have renewed interest in their functional diversity in homeostasis and disease. They are located within the human heart in the myocardium, in atherosclerotic plaques, in the aortic valve, and in close proximity to nerves. Their plasticity enables different and even opposite functions in response to changing t...
Source: Trends in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: Varricchi G, Marone G, Kovanen PT Tags: Trends Immunol Source Type: research

Group 2 Innate Lymphoid Cells Induce Antibody Production in Gastric Tissue.
Abstract A recent article published in Immunity by Naoko Satoh-Takayama et al. examines interactions between group 2 innate lymphocytes and gastric microbes that enhance IgA production. PMID: 32605803 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: Bando JK, Colonna M Tags: Trends Immunol Source Type: research

Instructing Memory in CD8+ Thymocytes.
Abstract T cells can sometimes acquire properties of a memory cell without encountering foreign antigen. Miller et al. now show that development of such 'memory phenotype' (MP) CD8+ T cells starts with recognition of self-ligands in the thymus, and finishes in peripheral tissues. These cells respond rapidly during infection, and infiltrate tumors, where they express high amounts of PD-1. PMID: 32518054 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 6, 2020 Category: Allergy & Immunology Authors: Ashby KM, Hogquist KA Tags: Trends Immunol Source Type: research

Where There's Smoke, There's Fire: Inflammation Drives MDS.
Abstract Chronic inflammation has been implicated in myelodysplastic syndrome (MDS); however, its role in disease progression is unclear. In a new study by Muto et al., MDS stem cells sparked with TRAF6-activated innate immune signaling were found to outcompete normal counterparts only when fueled by environmental inflammatory stimuli. Non-canonical NF-κB signaling is implicated in inflammatory synergy and MDS progression. PMID: 32513619 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 5, 2020 Category: Allergy & Immunology Authors: Datar GK, Goodell MA Tags: Trends Immunol Source Type: research

A Future Outlook on Molecular Mechanisms of Immunity.
PMID: 32507312 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 2, 2020 Category: Allergy & Immunology Authors: Weinmann AS, Youngblood BA, Smale ST, Brink R, Schatz DG, McHeyzer-Williams M Tags: Trends Immunol Source Type: research

A Synchronous IRF4-Dependent Gene Regulatory Network in B and Helper T Cells Orchestrating the Antibody Response.
We describe a conserved, likely ancient, gene regulatory network that intriguingly operates contemporaneously in B and CD4+ T cells to control their cell fate dynamics and thus, the character of the antibody response. The remarkable output of this network derives from graded expression, designated by antigen receptor signal strength, of a pivotal transcription factor that regulates alternate cell fate choices. PMID: 32467029 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 25, 2020 Category: Allergy & Immunology Authors: Cook SL, Franke MC, Sievert EP, Sciammas R Tags: Trends Immunol Source Type: research

Origins of the RAG Transposome and the MHC.
Abstract How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not be recognized by original TCR-like molecule(s), and new MHC-like gene(s) would be lost by neutral drift. Integrating recombination activating gene (RAG) transposon(s) in a TCR-like gene would result in greater r...
Source: Trends in Immunology - May 25, 2020 Category: Allergy & Immunology Authors: Tsakou-Ngouafo L, Paganini J, Kaufman J, Pontarotti P Tags: Trends Immunol Source Type: research

It Takes Three Receptors to Raise a B Cell.
Abstract As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint was previously modeled by the signaling of two opposing receptors, IL-7R and the pre-BCR. We provide an update to this model in which three receptors, IL-7R, pre-BCR, and CXCR4, work in concert to coordinate bot...
Source: Trends in Immunology - May 22, 2020 Category: Allergy & Immunology Authors: McLean KC, Mandal M Tags: Trends Immunol Source Type: research

Transcriptional Control of Mature B Cell Fates.
Abstract The mature naïve B cell repertoire consists of three well-defined populations: B1, B2 (follicular B, FOB), and marginal zone B (MZB) cells. FOB cells are the dominant mature B cell population in the secondary lymphoid organs and blood of both humans and mice. The driving forces behind mature B lineage selection have been linked to B cell receptor (BCR) signaling strength and environmental cues, but how these fate-determination factors are transcriptionally regulated remains poorly understood. We summarize emerging data on the role of transcription factors (TFs) - particularly the ETS and IRF families...
Source: Trends in Immunology - May 20, 2020 Category: Allergy & Immunology Authors: Wang H, Morse HC, Bolland S Tags: Trends Immunol Source Type: research

Editorial: Moving Pieces in Molecular Immunology.
e;n C PMID: 32405263 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 13, 2020 Category: Allergy & Immunology Authors: Sacristán C Tags: Trends Immunol Source Type: research

Resident Memory T Cells Escape 'Home Quarantine'.
CG Abstract T resident memory (Trm) cells provide a first line of defense in non-lymphoid tissues. A new report in Nature Immunology by Fonseca et al. reveals that CD8+ Trm cells can give rise to circulating effector and memory T cells, but remain predisposed to migrate back into their tissue of origin. PMID: 32386961 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 6, 2020 Category: Allergy & Immunology Authors: Künzli M, King CG Tags: Trends Immunol Source Type: research

The Speckled Protein (SP) Family: Immunity's Chromatin Readers.
Abstract Chromatin 'readers' are central interpreters of the epigenome that facilitate cell-specific transcriptional programs and are therapeutic targets in cancer and inflammation. The Speckled Protein (SP) family of chromatin 'readers' in humans consists of SP100, SP110, SP140, and SP140L. SPs possess functional domains (SAND, PHD, bromodomain) that dock to DNA or post-translationally modified histones and a caspase activation and recruitment domain (CARD) domain to promote multimerization. Mutations within immune expressed SPs associate with numerous immunological diseases including Crohn's disease, multiple sc...
Source: Trends in Immunology - May 5, 2020 Category: Allergy & Immunology Authors: Fraschilla I, Jeffrey KL Tags: Trends Immunol Source Type: research

Opportunities for Small Molecules in Cancer Immunotherapy.
Abstract Cancer immunotherapy has proven remarkably successful through instigation of systemic antitumor T cell responses. Despite this achievement, further advancements are needed to expand the scope of susceptible cancer types and overcome variation in treatment outcomes between patients. Small-molecule drugs targeting defined pathways and/or cells capable of immune modulation are expected to substantially improve efficacy of cancer immunotherapy. Small-molecule drugs possess unique properties compatible with systemic administration and amenable to both extracellular and intracellular targets. These compounds ca...
Source: Trends in Immunology - May 4, 2020 Category: Allergy & Immunology Authors: van der Zanden SY, Luimstra JJ, Neefjes J, Borst J, Ovaa H Tags: Trends Immunol Source Type: research

Inflammation and Skeletal Muscle Regeneration: Leave It to the Macrophages!
Abstract Inflammation is usually considered as harmful; however, it is also necessary for tissue recovery after injury. Macrophages exert immune and nonimmune functions throughout this process. During skeletal muscle regeneration, they mount an inflammatory response while exerting trophic roles on muscle and mesenchymal stem cells. Proinflammatory macrophages shift to being anti-inflammatory, triggering the resolution of inflammation. Studies have highlighted that during this shift, a crosstalk ensues, integrating cues for resolution, efferocytosis, cellular metabolism, and signaling pathways. During the restorati...
Source: Trends in Immunology - April 30, 2020 Category: Allergy & Immunology Authors: Chazaud B Tags: Trends Immunol Source Type: research

Circadian Influences of Diet on the Microbiome and Immunity.
Abstract Host circadian rhythmicity and the timing of feeding are increasingly recognized to cross-regulate and entrain each other, and may play crucial roles in regulating multiple physiological functions including host immunity and metabolic health. Of relevance, these circadian diet-immune interactions may be modulated by the gut microbiota. We review current knowledge linking the circadian clock and dietary timing to host immune-microbiota interactions, exemplifying how this axis may impact on host immunity in health and in a variety of immune-mediated diseases. We also discuss current challenges in reaching m...
Source: Trends in Immunology - April 28, 2020 Category: Allergy & Immunology Authors: Zheng D, Ratiner K, Elinav E Tags: Trends Immunol Source Type: research

Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses: (Trends in Immunology 41, 355-359; 2020).
PMID: 32362491 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 24, 2020 Category: Allergy & Immunology Authors: Jiang S, Hillyer C, Du L Tags: Trends Immunol Source Type: research

ILC3s: Rhythmic Keepers of Gut Integrity at Mealtime.
Abstract Cyclically, during the day, increased permeability of the intestinal epithelial barrier, allowing nutrient uptake, must be compensated for, to achieve increased protection against potentially harmful components. Seillet et al. demonstrate that, upon food intake, enteric neuron-derived VIP promotes anticipatory mucosal immunity by inducing ILC3s to produce protective IL-22. PMID: 32307240 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 16, 2020 Category: Allergy & Immunology Authors: Quatrini L, Moretta L, Mingari MC Tags: Trends Immunol Source Type: research

An Antiviral DNA Response without the STING?
Abstract Higher eukaryotes have evolved elegant and redundant pathways to protect their genomes from both genotoxic stressors and foreign DNA from invading pathogens. Emerging data from Burleigh et al. suggest that these distinct pathways may share factors to enhance the functional redundancy of both. PMID: 32305305 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 15, 2020 Category: Allergy & Immunology Authors: Meek K Tags: Trends Immunol Source Type: research

How Neutrophils Meet Their End.
Abstract Neutrophil death can transpire via diverse pathways and is regulated by interactions with commensal and pathogenic microorganisms, environmental exposures, and cell age. At steady state, neutrophil turnover and replenishment are continually maintained via a delicate balance between host-mediated responses and microbial forces. Disruptions in this equilibrium directly impact neutrophil numbers in circulation, cell trafficking, antimicrobial defenses, and host well-being. How neutrophils meet their end is physiologically important and can result in different immunologic consequences. Whereas nonlytic forms ...
Source: Trends in Immunology - April 14, 2020 Category: Allergy & Immunology Authors: Lawrence SM, Corriden R, Nizet V Tags: Trends Immunol Source Type: research

Remnant Epitopes Generating Autoimmunity: From Model to Useful Paradigm.
Abstract Autoimmune diseases are defined as pathologies of adaptive immunity by the presence of autoantibodies or MHC-restricted autoantigen-reactive T cells. Because autoreactivity is a normal process based on mechanisms producing repertoires of antibodies and T cell receptors, crucial questions about disease mechanisms and key steps for interference have been outstanding. We defined 25 years ago the 'remnant epitopes generate autoimmunity' (REGA)-model in which extracellular proteases from innate immune cells generate autoantigens. Here, we refine the REGA-model, tested in diseases ranging from organ-specific au...
Source: Trends in Immunology - April 13, 2020 Category: Allergy & Immunology Authors: Opdenakker G, Abu El-Asrar A, Van Damme J Tags: Trends Immunol Source Type: research

Noncanonical Functions of Antibodies.
Abstract The typical functions of antibodies are based on linking the process of antigen recognition with initiation of innate immune reactions. With the introduction of modern research technologies and the use of sophisticated model systems, recent years have witnessed the discovery of a number of noncanonical functions of antibodies. These functions encompass either untypical strategies for neutralization of pathogens or exertion of activities that are characteristic for other proteins (cytokines, chaperones, or enzymes). Here, we provide an overview of the noncanonical functions of antibodies and discuss their ...
Source: Trends in Immunology - April 6, 2020 Category: Allergy & Immunology Authors: Dimitrov JD, Lacroix-Desmazes S Tags: Trends Immunol Source Type: research

Breadth of Antibody Responses during Influenza Virus Infection and Vaccination.
Abstract Influenza viruses are a major public health problem, causing severe respiratory diseases. Vaccines offer the effective protective strategy against influenza virus infection. However, the systemic and adaptive immune responses to infection and vaccination are quite different. Inactivated vaccines are the best available countermeasure to induce effective antibodies against the emerged virus, but the response is narrow compared with potential breadth of virus infection. There is solid evidence to indicate that antibody responses to natural infection are relatively broad and exhibit quite different immunodomi...
Source: Trends in Immunology - April 4, 2020 Category: Allergy & Immunology Authors: Kubo M, Miyauchi K Tags: Trends Immunol Source Type: research

'Nervous' Immunity: Walking the Tightrope.
Abstract There is a major gap in our understanding of how the intestinal immune and nervous systems are integrated to regulate protective adaptations to enteric infections while maintaining tissue homeostasis. Three recent complementary reports published in Cell (2020) provide new mechanistic insights into how this enteric neuro-immune crosstalk may occur. PMID: 32249062 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 2, 2020 Category: Allergy & Immunology Authors: Kulkarni S, Kurapati S, Bogunovic M Tags: Trends Immunol Source Type: research

Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses.
Abstract Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs. PMID: 32249063 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 2, 2020 Category: Allergy & Immunology Authors: Jiang S, Hillyer C, Du L Tags: Trends Immunol Source Type: research

A20 and Cell Death-driven Inflammation.
Abstract A20 is a potent anti-inflammatory molecule, and mutations in TNFAIP3, the gene encoding A20, are associated with a wide panel of inflammatory pathologies, both in human and mouse. The anti-inflammatory properties of A20 are commonly attributed to its ability to suppress inflammatory NF-κB signaling by functioning as a ubiquitin-editing enzyme. However, A20 also protects cells from death, independently of NF-κB regulation, and recent work has demonstrated that cell death may drive some of the inflammatory conditions caused by A20 deficiency. Adding to the fact that the protective role of A20 do...
Source: Trends in Immunology - March 30, 2020 Category: Allergy & Immunology Authors: Priem D, van Loo G, Bertrand MJM Tags: Trends Immunol Source Type: research

Helper-like Innate Lymphoid Cells in Humans and Mice.
Abstract The innate lymphoid cell (ILC) family consists of natural killer (NK) cells, helper-like lymphoid cells (ILC1s, ILC2s, and ILC3s), and lymphoid tissue inducer (LTi) cells. Helper-like ILCs are considered the innate counterpart of T-helper cells because of similarities in their cytokine output and expression of key transcription factors. ILCs provide and regulate innate immune functions before the development of adaptive immunity. They are involved in host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. However, they can also be involved in inflammatory disorders and carc...
Source: Trends in Immunology - March 26, 2020 Category: Allergy & Immunology Authors: Guia S, Narni-Mancinelli E Tags: Trends Immunol Source Type: research

Immunotherapeutic Potential of TGF- β Inhibition and Oncolytic Viruses.
Immunotherapeutic Potential of TGF-β Inhibition and Oncolytic Viruses. Trends Immunol. 2020 Mar 26;: Authors: Groeneveldt C, van Hall T, van der Burg SH, Ten Dijke P, van Montfoort N Abstract In cancer immunotherapy, a patient's own immune system is harnessed against cancer. Immune checkpoint inhibitors release the brakes on tumor-reactive T cells and, therefore, are particularly effective in treating certain immune-infiltrated solid tumors. By contrast, solid tumors with immune-silent profiles show limited efficacy of checkpoint blockers due to several barriers. Recent discoveries highlight tran...
Source: Trends in Immunology - March 26, 2020 Category: Allergy & Immunology Authors: Groeneveldt C, van Hall T, van der Burg SH, Ten Dijke P, van Montfoort N Tags: Trends Immunol Source Type: research

SARS Coronavirus Redux.
Abstract As an atypical pneumonia began to appear in December 2019, Zhou et al. worked with remarkable speed to identify the associated virus, determine its relationship to animal viruses, and evaluate factors conferring infection susceptibility and resistance. These foundational results are being advanced to control the current worldwide human coronavirus epidemic. PMID: 32173256 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - March 12, 2020 Category: Allergy & Immunology Authors: Qing E, Gallagher T Tags: Trends Immunol Source Type: research

Are You There? Genetic Variation Impacts Long-Distance Connections in Diabetes.
Abstract A new study by Fasolino et al. defines how genetic variation in a mouse model of type 1 diabetes mellitus (T1DM) affects long-distance genomic interactions. The research has widespread implications for understanding how genetic diversity impacts disease susceptibility, and raises important concepts about mechanisms that can be influenced by genetic diversity between individuals. PMID: 32169284 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - March 10, 2020 Category: Allergy & Immunology Authors: Walter HC, Weinmann AS Tags: Trends Immunol Source Type: research

Type IIA Secreted Phospholipase A2 in Host Defense against Bacterial Infections.
Abstract The enzyme type IIA secreted phospholipase A2 (sPLA2-IIA) is crucial for mammalian innate host defense against bacterial pathogens. Most studies have investigated the role of sPLA2-IIA in systemic bacterial infections, identifying molecular pathways of bacterial resistance against sPLA2-IIA-mediated killing, and providing insight into sPLA2-IIA mechanisms of action. Sensitization of (antibiotic-resistant) bacteria to sPLA2-IIA action by blocking bacterial resistance or by applying sPLA2-IIA to treat bacterial infections might represent a therapeutic option in the future. Because sPLA2-IIA is highly expres...
Source: Trends in Immunology - March 6, 2020 Category: Allergy & Immunology Authors: van Hensbergen VP, Wu Y, van Sorge NM, Touqui L Tags: Trends Immunol Source Type: research

Next-Generation Neuroimmunology: New Technologies to Understand Central Nervous System Autoimmunity.
l H Abstract Understanding neuroimmunological disorders is essential for developing new diagnostic and therapeutic strategies. Rodent models have provided valuable insights, but are sometimes equated with their human counterparts. Here, we summarize how novel technologies may enable an improved human-focused view of immune mechanisms. Recent studies have applied these new technologies to the brain parenchyma, its surrounding cerebrospinal fluid, and peripheral immune compartments. Therapeutic interventions have also facilitated translational understanding in a reverse way. However, with improved technology, access...
Source: Trends in Immunology - March 5, 2020 Category: Allergy & Immunology Authors: Meyer Zu Hörste G, Gross CC, Klotz L, Schwab N, Wiendl H Tags: Trends Immunol Source Type: research

Neuroimmune Connections in Aging and Neurodegenerative Diseases.
Abstract In recent years, the inter-relationship between the innate immune system and the central nervous system (CNS) has moved to the forefront of biomedical research, with the discovery that these two physiological systems modulate each other by a steady mutual interaction. During normal brain aging, but also under certain pathological conditions, this crosstalk can go beyond physiological control, resulting in an unresolved inflammatory response of the CNS-resident immune cells that might initiate and propagate the progression of severe tissue damage and neurodegeneration. In this review, we focus on the impac...
Source: Trends in Immunology - March 5, 2020 Category: Allergy & Immunology Authors: Scheiblich H, Trombly M, Ramirez A, Heneka MT Tags: Trends Immunol Source Type: research

Deubiquitinases: Pro-oncogenic Activity and Therapeutic Targeting in Blood Malignancies.
Abstract Deubiquitinases are enzymes that remove ubiquitin moieties from the vast majority of cellular proteins, controlling their stability, interactions, and localization. The expression and activity of deubiquitinases are critical for physiology and can go awry in various diseases, including cancer. Based on recent findings in human blood cancers, we discuss the functions of selected deubiquitinases in acute leukemia and efforts to target these enzymes with the aim of blocking leukemia growth and improving disease outcomes. We focus on the emergence of the newest generation of preclinical inhibitors by discussi...
Source: Trends in Immunology - March 2, 2020 Category: Allergy & Immunology Authors: Gutierrez-Diaz BT, Gu W, Ntziachristos P Tags: Trends Immunol Source Type: research

Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment.
GJ Abstract Sialic acid sugar-carrying glycans, sialoglycans, are aberrantly expressed on many tumor cells and have emerged as potent regulatory molecules involved in creating a tumor-supportive microenvironment. Sialoglycans can be recognized by sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immunomodulatory receptors. Most mammalian Siglecs transmit inhibitory signals comparable with the immune checkpoint inhibitor programmed death protein 1 (PD-1), but some are activating. Recent studies have shown that tumor cells can exploit sialoglycan-Siglec interactions to modulate immune cell func...
Source: Trends in Immunology - March 2, 2020 Category: Allergy & Immunology Authors: van de Wall S, Santegoets KCM, van Houtum EJH, Büll C, Adema GJ Tags: Trends Immunol Source Type: research

The Fetal-Maternal Immune Interface in Uterus Transplantation.
Abstract Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a unique clinical and experimental model. We posit that understanding the distinct immunological properties at the int...
Source: Trends in Immunology - March 1, 2020 Category: Allergy & Immunology Authors: Iske J, Elkhal A, Tullius SG Tags: Trends Immunol Source Type: research

CD38: Modulating Histone Methyltransferase EZH2 Activity in SLE.
Abstract To keep autoreactive T cells under control in SLE patients, immunosuppressive regimens are used, which can increase susceptibility to bacterial and viral infections. Recently, Katsuyama et al., demonstrated that the CD38/NAD/Sirtuin1/EZH2 axis reduces cytolytic CD8+ T cell function and might be targeted to overcome incidence of infections. PMID: 32061543 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - February 12, 2020 Category: Allergy & Immunology Authors: Chakraborty P, Mehrotra S Tags: Trends Immunol Source Type: research

Maternal Leukocytes and Infant Immune Programming during Breastfeeding.
Abstract The fetal immune system develops in a rather sterile environment relative to the outside world and, therefore, lacks antigenic education. Soon after birth, the newborn is exposed to the hostile environment of pathogens. Recently, animal- and limited human-based studies have indicated that help from the mother, upon transfer of leukocytes and their products via breast milk feeding, greatly assists the newborn's immune system. Here, I discuss the newest advances on how milk leukocytes impact early life immunity, with an emphasis on the development of the infant T cell repertoire and early immune responses i...
Source: Trends in Immunology - February 10, 2020 Category: Allergy & Immunology Authors: Laouar A Tags: Trends Immunol Source Type: research

Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity.
Abstract AT-rich interactive domain 5A (ARID5A/Arid5a) is a known cofactor of transcription factors (TFs) that contributes to cell growth and differentiation. It has recently been recognized for its unique function in the stabilization of mRNA, which is associated with inflammatory autoimmune diseases. Studies have revolutionized our understanding of the post-transcriptional regulation of inflammatory genes by revealing the fundamental events underpinning novel functions and activities of Arid5a. We review current research on Arid5a, which has focused our attention towards the therapeutic potential of this factor ...
Source: Trends in Immunology - February 5, 2020 Category: Allergy & Immunology Authors: Nyati KK, Zaman MM, Sharma P, Kishimoto T Tags: Trends Immunol Source Type: research

T Cell Co-stimulation and Functional Modulation by Innate Signals.
Abstract Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), play a pivotal role in the initiation of innate immune responses. Certain PRRs are also expressed by CD4+ and CD8+ T cells, where they function to provide co-stimulatory signals for their activation and differentiation. Recently, stimulator of interferon genes (STING) was found to be highly expressed in CD4+ and CD8+ T cells and to modulate T cell function. STING signaling inhibits cell growth and stimulates type I interferon (IFN-I) responses in T cells through reciprocal ...
Source: Trends in Immunology - February 5, 2020 Category: Allergy & Immunology Authors: Imanishi T, Saito T Tags: Trends Immunol Source Type: research

Taking Insect Immunity to the Single-Cell Level.
Abstract For decades, insect immunology has contributed groundbreaking discoveries on the intricacies of innate immunity. These discoveries have profoundly impacted our understanding of innate immunology in mammalian systems and improved human therapeutic interventions, from the composition of vaccines to cell-based immune therapies. Current knowledge of insect immunity mainly encompasses detailed molecular mechanisms and systemic responses to pathogen infection. However, the organs and specific cell populations involved in immune responses remain elusive. Here, we highlight the need for a better understanding of ...
Source: Trends in Immunology - February 5, 2020 Category: Allergy & Immunology Authors: Merkling SH, Lambrechts L Tags: Trends Immunol Source Type: research

Dynamic Post-Transcriptional Events Governing CD8+ T Cell Homeostasis and Effector Function.
Abstract Effective T cell responses against infections and tumors require a swift and ample production of cytokines, chemokines, and cytotoxic molecules. The production of these effector molecules relies on rapid changes of gene expression, determined by cell-intrinsic signals and environmental cues. Here, we review our current understanding of gene-specific regulatory networks that define the magnitude and timing of cytokine production in CD8+ T cells. We discuss the dynamic features of post-transcriptional control during CD8+ T cell homeostasis and activation, and focus on the crosstalk between cell signaling an...
Source: Trends in Immunology - January 29, 2020 Category: Allergy & Immunology Authors: Salerno F, Turner M, Wolkers MC Tags: Trends Immunol Source Type: research

Nuclear Receptors in Cancer Inflammation and Immunity.
ou S Abstract Members of the nuclear receptor (NR) superfamily orchestrate cellular processes that can impact on numerous cancer hallmarks. NR activity plays important roles in the tumor microenvironment by controlling inflammation and immune responses. We summarize recent insights into the diverse mechanisms by which NR activity can control tumor inflammation, the roles of different NRs in modulating tumor immunity, and the biological features of immune cells that express specific NRs in the context of cancer. NR-dependent alterations in tumor inflammation and immunity may be amenable to pharmacological manipulat...
Source: Trends in Immunology - January 22, 2020 Category: Allergy & Immunology Authors: Zhao L, Hu H, Gustafsson JÅ, Zhou S Tags: Trends Immunol Source Type: research

Key Roles of MiT Transcription Factors in Innate Immunity and Inflammation.
Abstract Microphthalmia/TFE (MiT) transcription factors (TFs), such as transcription factor EB (TFEB) and transcription factor E3 (TFE3), are emerging as key regulators of innate immunity and inflammation. Rapid progress in the field requires a focused update on the latest advances. Recent studies show that TFEB and TFE3 function in innate immune cells to regulate antibacterial and antiviral responses downstream of phagocytosis, interferon (IFN)-γ, lipopolysaccharide (LPS), and adenosine receptors. Moreover, overexpression of TFEB or TFE3 can drive inflammation in vivo, such as in atherosclerosis, while in o...
Source: Trends in Immunology - January 17, 2020 Category: Allergy & Immunology Authors: Irazoqui JE Tags: Trends Immunol Source Type: research

Metabolic Adaptations to Infections at the Organismal Level.
Abstract Metabolic processes occurring during host-microbiota-pathogen interactions can favorably or negatively influence host survival during infection. Defining the metabolic needs of the three players, the mechanisms through which they acquire nutrients, and whether each participant cooperates or competes with each other to meet their own metabolic demands during infection has the potential to reveal new approaches to treat disease. Here, we review topical findings in organismal metabolism and infection and highlight four emerging lines of investigation: how host-microbiota metabolic partnerships protect agains...
Source: Trends in Immunology - January 17, 2020 Category: Allergy & Immunology Authors: Troha K, Ayres JS Tags: Trends Immunol Source Type: research

Skin-Resident Innate Lymphoid Cells - Cutaneous Innate Guardians and Regulators.
Abstract Skin is the largest barrier organ and an important interface between the body and the outside environment. Immune surveillance and homeostatic regulation of skin function are governed by complex interactions between resident lymphoid and myeloid cells and their communications with the surrounding parenchyma. Recent studies have provided exciting insights about the unique characteristics of skin-resident innate lymphoid cells (ILCs). Here, we discuss advances demonstrating how skin ILCs contribute to tissue homeostasis by regulating microbiome balance in steady-state and how their dysregulation can trigger...
Source: Trends in Immunology - January 14, 2020 Category: Allergy & Immunology Authors: Kobayashi T, Ricardo-Gonzalez RR, Moro K Tags: Trends Immunol Source Type: research

Mitochondrial and Purinergic Dysregulation Promote Abnormal Behavior in Mice.
Abstract Increasing evidence implicates immune dysregulation in the development of neurological disorders. Recent research by Fan and colleagues deepens our understanding of how physical stress alters the immune system to promote anxiety-like behavior. PMID: 31948872 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - January 13, 2020 Category: Allergy & Immunology Authors: Fang P, Hsiao EY Tags: Trends Immunol Source Type: research

ACLY-matizing Macrophages to Histone Modification during Immunometabolic Reprogramming.
Abstract Metabolic reprogramming in macrophages supports effector functions and differs depending on the activating stimulus. Lauterbach et al. now show that early metabolic alterations in macrophages driven by LPS signaling serve to increase the acetyl-CoA pool via citrate metabolism by the ATP-citrate lyase (ACLY), leading to histone acetylation and regulation of TLR-driven gene expression. PMID: 31948874 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - January 13, 2020 Category: Allergy & Immunology Authors: Williams NC, O'Neill LA Tags: Trends Immunol Source Type: research

Human Secretory IgM: An Elusive Player in Mucosal Immunity.
Abstract Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a key role in establishing and promoting commensal gut tolerance in mice and humans. The true interactions between SIgMs and the microbiota remain controversial and we aim to consolidate current knowledge in this review. Through comprehensive examination of SIgMs and their corresponding B cell secretors in several different pathological immunological contexts, we review the presumed role of these molecules in gut tolerance, inflammatory bowel...
Source: Trends in Immunology - January 9, 2020 Category: Allergy & Immunology Authors: Michaud E, Mastrandrea C, Rochereau N, Paul S Tags: Trends Immunol Source Type: research

Control of Stimulus-Dependent Responses in Macrophages by SWI/SNF Chromatin Remodeling Complexes.
Abstract Epigenetic regulation plays an important role in controlling the activation, timing, and resolution of innate immune responses in macrophages. Previously, SWI/SNF chromatin remodeling was found to define the kinetics and selectivity of gene activation in response to microbial ligands; however, these studies do not reflect a comprehensive understanding of SWI/SNF complex regulation. In 2018, a new variant of the SWI/SNF complex was identified with unknown function in inflammatory gene regulation. Here, we summarize the biochemical and genomic properties of SWI/SNF complex variants and the potential for inc...
Source: Trends in Immunology - January 9, 2020 Category: Allergy & Immunology Authors: Gatchalian J, Liao J, Maxwell MB, Hargreaves DC Tags: Trends Immunol Source Type: research