TREM1 Blockade: Killing Two Birds with One Stone.
Abstract Infectious and sterile injuries cause the release of PAMPs and DAMPs. A study by Liu et al. (Nat. Immunol. 2019) reports that DAMP-induced sterile brain inflammation from stroke is associated with sympathetic nervous system activation, enhancing intestinal permeability, the release of microbiota-derived PAMPs, and inflammation. TREM1 is implicated as a potential target to treat stroke and DAMP- and PAMP-induced inflammation. PMID: 31439414 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - August 20, 2019 Category: Allergy & Immunology Authors: Colonna M Tags: Trends Immunol Source Type: research

Interferon Control of Neurotropic Viral Infections.
Abstract Interferons (IFNs) comprise a pleiotropic family of signaling molecules that are often the first line of defense against viral infection. Inflammatory responses induced by IFN are generally well tolerated during peripheral infections; yet, the same degree of inflammation during infection of the central nervous system (CNS) could be catastrophic. Thus, IFN responses must be modified within the CNS to ensure host survival. In this review, we discuss emerging principles highlighting unique aspects of antiviral effects of IFN protection following neurotropic viral infection, chiefly using new techniques in ro...
Source: Trends in Immunology - August 19, 2019 Category: Allergy & Immunology Authors: Milora KA, Rall GF Tags: Trends Immunol Source Type: research

Old T Cells Interfer(on) with Neurogenesis.
Abstract Adult neurogenesis plays an important role in brain function and declines with aging. A recent report demonstrates clonal T cell expansion within neurogenic niches of the aged brain, impairing neurogenesis through IFNγ signaling (Dulken et al.,Nature, 2019). These results highlight T cells as important contributors to and potential therapeutic targets for age-related brain dysfunction. PMID: 31422900 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - August 15, 2019 Category: Allergy & Immunology Authors: Rustenhoven J, Herz J, Kipnis J Tags: Trends Immunol Source Type: research

Macrophage Plasticity and Function in the Eye and Heart.
Abstract Macrophages are important mediators of inflammation and tissue remodeling. Recent insights into the heterogeneity of macrophage subpopulations have renewed interest in their functional diversity in homeostasis and disease. In addition, their plasticity enables them to perform a variety of functions in response to changing tissue contexts, such as those imposed by aging. These qualities make macrophages particularly intriguing cells given their dichotomous role in protecting against, or accelerating, diseases of the cardiovascular system and the eye, two tissues that are particularly susceptible to the eff...
Source: Trends in Immunology - August 15, 2019 Category: Allergy & Immunology Authors: Wang Z, Koenig AL, Lavine KJ, Apte RS Tags: Trends Immunol Source Type: research

3D Chromosomal Landscapes in Hematopoiesis and Immunity.
Abstract Epigenetic dysregulation plays a profound role in the pathogenesis of hematological malignancies, which is often the result of somatic mutations of chromatin regulators. Previously, these mutations were largely considered to alter gene expression in two dimensions, by activating or repressing chromatin states; however, research in the last decade has highlighted the increasing impact of the 3D organization of the genome in gene regulation and disease pathogenesis. Here, we summarize the current principles of 3D chromatin organization, how the integrity of the 3D genome governs immune cell development and ...
Source: Trends in Immunology - August 15, 2019 Category: Allergy & Immunology Authors: Kloetgen A, Thandapani P, Tsirigos A, Aifantis I Tags: Trends Immunol Source Type: research

Opening the Window of Immune Opportunity: Treating Childhood Asthma.
Abstract Asthma is an increasingly common childhood disease and although most patients can control their symptoms with medication, a proportion experience life-threatening symptoms. The advent of novel biologic therapies represents a giant leap forward for asthma treatment, but efficacy is rarely tested in children. Recent mechanistic work in mice suggests that early life is a key period for immune development and, therefore, allergen sensitization. Although children with severe asthma experience significant comorbidities and are at increased risk for serious diseases such as chronic obstructive pulmonary disease ...
Source: Trends in Immunology - August 14, 2019 Category: Allergy & Immunology Authors: Lloyd CM, Saglani S Tags: Trends Immunol Source Type: research

ABIN-2, of the TPL-2 Signaling Complex, Modulates Mammalian Inflammation.
Abstract Mammalian TPL-2 kinase (MAP3K8) mediates Toll-like receptor activation of ERK1/2 and p38α MAP kinases and is critical for regulating immune responses to pathogens. TPL-2 also has an important adaptor function, maintaining stability of associated ABIN-2 ubiquitin-binding protein. Consequently, phenotypes detected in Map3k8-/- mice can be caused by lack of TPL-2, ABIN-2, or both proteins. Recent studies show that increased inflammation of Map3k8-/- mice in allergic airway inflammation and colitis results from reduced ABIN-2 signaling, rather than blocked TPL-2 signaling. However, Map3k8-/- mice have b...
Source: Trends in Immunology - August 7, 2019 Category: Allergy & Immunology Authors: Webb LV, Ventura S, Ley SC Tags: Trends Immunol Source Type: research

Innate Immune Control of Adipose Tissue Homeostasis.
Abstract Adipose tissue is a critical regulator of systemic metabolism and normal bodily homeostasis. Recently, the immune system has been implicated in the regulation of adipose tissue homeostasis and function. Here, we highlight new insights into the distinct phenotypes and functions of adipose resident leukocytes, including a growing body of work on their role in adipose tissue remodeling and thermogenesis. We discuss how the protective capacity of the adipose immune system can be diminished during obesity, where immune cells promote sterile inflammation leading to insulin resistance. Understanding the role of ...
Source: Trends in Immunology - August 6, 2019 Category: Allergy & Immunology Authors: Kane H, Lynch L Tags: Trends Immunol Source Type: research

Modulation of Innate Immunity by Amyloidogenic Peptides.
Abstract Amyloid formation contributes to the development of progressive metabolic and neurodegenerative diseases, while also serving functional roles in host defense. Emerging evidence suggests that as amyloidogenic peptides populate distinct aggregation states, they interact with different combinations of pattern recognition receptors (PRRs) to direct the phenotype and function of tissue-resident and infiltrating innate immune cells. We review recent evidence of innate immunomodulation by distinct forms of amyloidogenic peptides produced by mammals (humans, non-human primates), bacteria, and fungi, as well as th...
Source: Trends in Immunology - July 15, 2019 Category: Allergy & Immunology Authors: Westwell-Roper C, Verchere CB Tags: Trends Immunol Source Type: research

Transposons to V(D)J Recombination: Evolution of the RAG Reaction.
Abstract Evolutionarily, how RAG endonucleases in vertebrate immune systems could shed dangerous transposon-like propensities, and instead, support the organized assembly of antigen receptor variable domains, has been unclear. Recent structural work by Schatz and colleagues (Nature, 2019) identifies features of the RAG endonuclease deemed to be key in supporting this critical change in vertebrate advancement. PMID: 31307890 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - July 13, 2019 Category: Allergy & Immunology Authors: Lieber MR Tags: Trends Immunol Source Type: research

Dendritic Cell Metabolism and Function in Tumors.
Abstract Dendritic cells (DCs) are fundamental for the initiation and maintenance of immune responses against malignant cells. Despite the unique potential of DCs to elicit robust anticancer immunity, the tumor microenvironment poses a variety of challenges that hinder competent DC function and consequently inhibit the development of protective immune responses. Here, we discuss recent studies uncovering new molecular pathways and metabolic programs that tumors manipulate in DCs to disturb their homeostasis and evade immune control. We also examine certain state-of-the-art strategies that seek to improve DC functi...
Source: Trends in Immunology - July 10, 2019 Category: Allergy & Immunology Authors: Giovanelli P, Sandoval TA, Cubillos-Ruiz JR Tags: Trends Immunol Source Type: research

Computational and Systems Immunology: A Student's Perspective.
Abstract The big data revolution has transformed the landscape of immunology research. As inaugural students of Stanford's new Computational and Systems Immunology PhD track, we share our experiences and advice with other institutions considering a similar program. PMID: 31288986 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - July 6, 2019 Category: Allergy & Immunology Authors: Good Z, Glanville J, Gee MH, Davis MM, Khatri P Tags: Trends Immunol Source Type: research

Granulopoiesis and Neutrophil Homeostasis: A Metabolic, Daily Balancing Act.
Abstract Granulopoiesis is part of the hematopoietic hierarchic architecture, where hematopoietic stem cells give rise to highly proliferative multipotent and lineage-committed granulocytic progenitor cells that differentiate into unipotent neutrophil progenitors. Given their short lifespan, neutrophils are rapidly cleared from circulation through specialized efferocytic macrophages. Together with an intrinsic clock, these processes contribute to circadian fluctuations, preserving self-tolerance and protection against invading pathogens. However, metabolic perturbation of granulopoiesis and neutrophil homeostasis ...
Source: Trends in Immunology - July 1, 2019 Category: Allergy & Immunology Authors: Yvan-Charvet L, Ng LG Tags: Trends Immunol Source Type: research

Tissue-Resident Memory T Cells in Cancer Immunosurveillance.
Abstract Following their activation and expansion in response to foreign threats, many T cells are retained in peripheral tissues without recirculating in the blood. These tissue-resident CD8+ memory T (TRM) cells patrol barrier surfaces and nonlymphoid organs, where their critical role in protecting against viral and bacterial infections is well established. Recent evidence suggests that TRM cells also play a vital part in preventing the development and spread of solid tumors. Here, we discuss the emerging role of TRM cells in anticancer immunity. We highlight defining features of tumor-localizing TRM cells, exam...
Source: Trends in Immunology - June 26, 2019 Category: Allergy & Immunology Authors: Park SL, Gebhardt T, Mackay LK Tags: Trends Immunol Source Type: research

Towards Immunotherapy for Pediatric Brain Tumors.
Abstract Pediatric brain tumors are the leading cause of childhood cancer-related death. Immunotherapy is a powerful new approach for treating some refractory cancers; applying this 'fourth pillar' of cancer treatment to pediatric brain tumors is an exciting but challenging prospect. This review offers new perspectives on moving towards successful immunotherapy for pediatric brain tumors, focusing on pediatric high-grade glioma (HGG), a subgroup with universally poor outcomes. We cover chimeric antigen receptor T cell (CAR-T) therapy, vaccine therapy, and checkpoint inhibition in this context, and focus on the nee...
Source: Trends in Immunology - June 19, 2019 Category: Allergy & Immunology Authors: Wang SS, Bandopadhayay P, Jenkins MR Tags: Trends Immunol Source Type: research

The Rise of Plant Resistosomes.
Abstract Both plants and animals carry NOD-like-receptors (NLRs). However, the formation of inflammasome-like structures in plants has been an open question for many years. Two recent publications (Wang et al.Science, 2019) report key findings regarding the structure and activation of plant 'resistosomes', and provide insights into the control of programmed cell death in plants. PMID: 31182341 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 7, 2019 Category: Allergy & Immunology Authors: Mermigka G, Sarris PF Tags: Trends Immunol Source Type: research

The Immunomodulatory Potential of the Metabolite Itaconate.
Abstract The field of immunometabolism has demonstrated that metabolites can lead double lives as immunomodulators. Itaconate is perhaps the best example of such a moonlighting molecule, and has been shown to have multiple anti-inflammatory effects in macrophages. Itaconate is significantly upregulated under inflammatory conditions, and can promote an anti-inflammatory phenotype by reducing oxidative stress and blocking transcriptional responses to lipopolysaccharide (LPS) in murine macrophages. Antibacterial and protumor effects have also been described for itaconate and, most recently, reports have surfaced of i...
Source: Trends in Immunology - June 6, 2019 Category: Allergy & Immunology Authors: Hooftman A, O'Neill LAJ Tags: Trends Immunol Source Type: research

Neutrophils Are on a Roll.
e;n C PMID: 31175061 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 5, 2019 Category: Allergy & Immunology Authors: Sacristán C Tags: Trends Immunol Source Type: research

Neutrophil Recruitment: From Model Systems to Tissue-Specific Patterns.
Abstract Neutrophil recruitment is not only vital for host defense, but also relevant in pathological inflammatory reactions, such as sepsis. Model systems have been established to examine different steps of the leukocyte recruitment cascade in vivo and in vitro under inflammatory conditions. Recently, tissue-specific recruitment patterns have come into focus, requiring modification of formerly generalized assumptions. Here, we summarize existing models of neutrophil recruitment and highlight recent discoveries in organ-specific recruitment patterns. New techniques show that previously stated assumptions of integr...
Source: Trends in Immunology - June 4, 2019 Category: Allergy & Immunology Authors: Margraf A, Ley K, Zarbock A Tags: Trends Immunol Source Type: research

Neutrophil Diversity in Health and Disease.
Abstract New evidence has challenged the outdated dogma that neutrophils are a homogeneous population of short-lived cells. Although neutrophil subpopulations with distinct functions have been reported under homeostatic and pathological conditions, a full understanding of neutrophil heterogeneity and plasticity is currently lacking. We review here current knowledge of neutrophil heterogeneity and diversity, highlighting the need for deep genomic, phenotypic, and functional profiling of the identified neutrophil subpopulations to determine whether these cells truly represent bona fide novel neutrophil subsets. We s...
Source: Trends in Immunology - May 31, 2019 Category: Allergy & Immunology Authors: Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P Tags: Trends Immunol Source Type: research

The Healing Power of Neutrophils.
Abstract Neutrophils promptly accumulate in large numbers at sites of tissue injury. Injuries to the skin or mucosae disrupt barriers against the external environment, and the bactericidal actions of neutrophils are important in preventing microbial invasion. Neutrophils have also been associated with exacerbated inflammation, for example in non-healing wounds or in conditions such as inflammatory bowel disease (IBD). However, additional neutrophil functions important for angiogenesis and tissue restoration have been uncovered in models of sterile and ischemic injury, as well as in tumors. These functions are also...
Source: Trends in Immunology - May 31, 2019 Category: Allergy & Immunology Authors: Phillipson M, Kubes P Tags: Trends Immunol Source Type: research

Biological Roles of Neutrophil-Derived Granule Proteins and Cytokines.
n O Abstract Neutrophils, the most abundant white blood cells in human circulation, entertain intense interactions with other leukocyte subsets, platelets, and stromal cells. Molecularly, such interactions are typically communicated through proteins generated during granulopoiesis, stored in granules, or produced on demand. Here, we provide an overview of the mammalian regulation of granule protein production in the bone marrow and the de novo synthesis of cytokines by neutrophils recruited to tissues. In addition, we discuss some of the known biological roles of these protein messengers, and how neutrophil-borne ...
Source: Trends in Immunology - May 30, 2019 Category: Allergy & Immunology Authors: Cassatella MA, Östberg NK, Tamassia N, Soehnlein O Tags: Trends Immunol Source Type: research

The Neutrophil Life Cycle.
Abstract Neutrophils are recognized as an essential part of the innate immune response, but an active debate still exists regarding the life cycle of these cells. Neutrophils first differentiate in the bone marrow through progenitor intermediaries before entering the blood, in a process that gauges the extramedullary pool size. Once believed to be directly eliminated in the marrow, liver, and spleen, neutrophils, after circulating for less than 1 day, are now known to redistribute into multiple tissues with poorly understood kinetics. In this review, we provide an update on the dynamic distribution of neutrophils ...
Source: Trends in Immunology - May 29, 2019 Category: Allergy & Immunology Authors: Hidalgo A, Chilvers ER, Summers C, Koenderman L Tags: Trends Immunol Source Type: research

cDC1s: New Orchestrators of Tissue Innate Immunity.
Abstract Type-I conventional dendritic cells (cDC1s) are key in inducing adaptive immunity. Using single-cell sequencing, Ginhoux and colleagues (Immunity 2019;50:1069-1083.e8) find that a subset of activated cDC1s in bacteria-infected skin is critical for neutrophil recruitment via the production of VEGF-α. These results reveal a crucial function for cDC1s beyond antigen presentation. PMID: 31133464 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Del Fresno C, Sancho D Tags: Trends Immunol Source Type: research

Neutrophil Research, Quo Vadis?
Abstract In recent years, great progress has been made to understand how neutrophils contribute to homeostatic regulation, tumor progression, and chronic inflammation. Here, I highlight a few salient basic questions to be addressed in the field. Ideally, future investigations along these lines can contribute to identifying possible means of therapeutically interfering with neutrophil effector functions to fine-tune innate immunity. PMID: 31133465 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Soehnlein O Tags: Trends Immunol Source Type: research

Microglia and Neutrophils to the Rescue.
Abstract Invasive candidiasis is a medical condition that is challenging to treat. A recent study (Drummond et al.Nat. Immunol. 2019;20:559-570) reveals new insights into the role of microglia and neutrophils in limiting fungal dissemination to the mouse brain. Gaining knowledge into tissue-specific protection mechanisms may ensure improved prognosis and disease management against fungal infections. PMID: 31133466 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Gadjeva M Tags: Trends Immunol Source Type: research

Notch Signaling Orchestrates Helminth-Induced Type 2 Inflammation.
Abstract Infection with helminth parasites poses a significant challenge to the mammalian immune system. The type 2 immune response to helminth infection is critical in limiting worm-induced tissue damage and expelling parasites. Conversely, aberrant type 2 inflammation can cause debilitating allergic disease. Recent studies have revealed that key type 2 inflammation-associated immune and epithelial cell types respond to Notch signaling, broadly regulating gene expression programs in cell development and function. Here, we discuss new advances demonstrating that Notch is active in the development, recruitment, loc...
Source: Trends in Immunology - May 15, 2019 Category: Allergy & Immunology Authors: Webb LM, Tait Wojno ED Tags: Trends Immunol Source Type: research

Partners in Crime: Neutrophil-CTC Collusion in Metastasis.
Abstract A recent study in Nature (Szczerba et al. 2019;566:553-557) reports that the association of neutrophils with circulating tumor cells (CTCs) in the blood of patients with breast cancer can promote CTC proliferation and metastasis. These findings reveal a new mechanism by which the innate immune system may be co-opted to drive tumor progression. PMID: 31101536 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 14, 2019 Category: Allergy & Immunology Authors: Guo B, Oliver TG Tags: Trends Immunol Source Type: research

Regulatory Immune Mechanisms beyond Regulatory T Cells.
Abstract In autoimmunity, aggressive immune responses are counteracted by suppressive rejoinders. For instance, FOXP3-expressing regulatory T cells (Tregs), have shown remarkable effects in limiting autoimmunity in preclinical models. However, early results from human Treg trials have not been as positive. Here, we highlight questions surrounding Treg transfers as putative treatments for autoimmunity. We discuss whether lack of antigenic recognition might be key to shifting cells from contributing to an aggressive autoresponse, to being part of a regulatory network. Moreover, we argue that identifying the physiolo...
Source: Trends in Immunology - May 14, 2019 Category: Allergy & Immunology Authors: Christoffersson G, von Herrath M Tags: Trends Immunol Source Type: research

The Yellow Brick Road towards HIV Eradication.
n M Abstract A London patient living with HIV-1 has become the second person to achieve remission from HIV-1 infection for>1 year after receiving a bone marrow stem cell transplant from a donor with cells resistant to CCR5-tropic HIV-1 infection (Gupta et al. Nature 2019;568:244-248). This case provides important clues in the uncertain path towards an HIV cure. PMID: 31072685 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Saez-Cirion A, Müller-Trutwin M Tags: Trends Immunol Source Type: research

Monocytes Inadequately Fill In for Meningeal Macrophages.
Abstract In the meninges, a unique subset of tissue-resident macrophages serves as a sentinel population against invading microorganisms while suppressing harmful inflammation. A recent report shows that when murine meningeal macrophages are killed by viruses, circulating monocytes repopulate the open niche. However, they fail to mimic all aspects of tissue-resident macrophages. PMID: 31072686 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Song E, Iwasaki A Tags: Trends Immunol Source Type: research

Dengue and Zika: The Complexities of Being Related.
Abstract Following the recent Zika virus (ZIKV) outbreak in the Americas, a major question that has arisen is how dengue virus (DENV) immunity impacts Zika virus infection and disease. A recent study (Rodriguez-Barraquer, I. et al. Science 2019;363:607-610) shows that DENV immunity is, for the most part, protective against ZIKV, but exceptions may exist. PMID: 31072687 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Krammer F, Lim JK Tags: Trends Immunol Source Type: research

Antibodies Tip the Balance Towards an HIV Cure.
Abstract Long-term drug therapy for HIV-1 infection can prevent both disease progression and virus transmission, but treatment does not eradicate the virus. A new gene therapy study (Immunity 2019;50:567-575.e5) using human antibodies shows significant promise for a functional cure in a non-human primate model. PMID: 31030743 [PubMed - in process] (Source: Trends in Immunology)
Source: Trends in Immunology - May 1, 2019 Category: Allergy & Immunology Authors: Haigwood NL, Hessell AJ Tags: Trends Immunol Source Type: research

Leukocyte Adhesion: Reconceptualizing Chemokine Presentation by Glycosaminoglycans.
Abstract Recruitment of immune cells from the vasculature relies on the presentation of glycosaminoglycan-bound chemokines on the luminal side of vascular endothelial cells. However, the current model of chemokine-glycosaminoglycan interactions, and its implications for receptor interactions, remains poorly developed. We propose a refined 'Chemokine Cloud' model, arguing that chemokines are not presented to leukocytes bound to glycosaminoglycans, but rather, in solution while sequestered within the hydrated glycocalyx. We posit that glycosaminoglycans provide an immobilized chemokine depot maintaining a 'cloud' of...
Source: Trends in Immunology - April 18, 2019 Category: Allergy & Immunology Authors: Graham GJ, Handel TM, Proudfoot AEI Tags: Trends Immunol Source Type: research

Cell Death and Inflammation - A Vital but Dangerous Liaison.
Abstract The immune system has developed multiple ways to fight infection. Yet, it is constantly tasked with overcoming newly developing pathogenic mechanisms of resistance to host immunity. In most mammals, the stimulation of both innate and adaptive immune receptors can result in gene activation and cell death induction by apoptosis and necroptosis. RIPK1 and RIPK3 are key mediators of necroptosis; however, new findings support their role in the regulation of cell death-independent proinflammatory signaling. We discuss here the biological functions of RIPK1 and RIPK3, how they regulate cell death and inflammatio...
Source: Trends in Immunology - April 16, 2019 Category: Allergy & Immunology Authors: Peltzer N, Walczak H Tags: Trends Immunol Source Type: research

Cancer Immunoediting by Innate Lymphoid Cells.
Abstract The immune system plays a dual role in cancer. It conveys protective immunity but also facilitates malignant progression, either by sculpting tumor immunogenicity or by creating a microenvironment that can stimulate tumor outgrowth or aid in a subsequent metastatic cascade. Innate lymphoid cells (ILCs) embody this functional heterogeneity, although the nature of their responses in cancer has only recently begun to be unveiled. We provide an overview of recent insights into the role of ILCs in cancer. We also discuss how ILCs fit into the conceptual framework of cancer immunoediting, which integrates the d...
Source: Trends in Immunology - April 13, 2019 Category: Allergy & Immunology Authors: Wagner M, Koyasu S Tags: Trends Immunol Source Type: research

PD-1 Tumor Suppressor Signaling in T Cell Lymphomas.
Abstract The inhibitory receptor PD-1 is critical to balancing antigen-induced T cell activation; its inhibition is currently being explored to enhance antitumor T cell immunity with certain successful outcomes. However, PD-1 has also emerged as a central tumor suppressor in T cell lymphomas, where the tumor cell originates from a T cell itself. These aggressive cancers are frequently characterized by oncogenic mutations in T cell receptor (TCR) signaling pathways. PD-1 activity within malignant T cells can negatively regulate the PI3K/AKT and PKCθ/NF-κB tumor survival pathways and PD-1 is frequently i...
Source: Trends in Immunology - April 9, 2019 Category: Allergy & Immunology Authors: Wartewig T, Ruland J Tags: Trends Immunol Source Type: research

Rediscovering MIF: New Tricks for an Old Cytokine.
Abstract Produced by many cell types, macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with critical and supporting roles in many disease states and conditions. Its disease associations, myriad functions, receptors, and downstream signaling have been the subject of considerable research, yet many questions remain. Moreover, the relevance of MIF's partially functionally redundant family member, D-dopachrome tautomerase (D-DT), also remains to be further characterized. Here, we discuss recent discoveries demonstrating direct roles of MIF in supporting NLR Family Pyrin Domain-Containing 3 (NRLP3...
Source: Trends in Immunology - April 5, 2019 Category: Allergy & Immunology Authors: Harris J, VanPatten S, Deen NS, Al-Abed Y, Morand EF Tags: Trends Immunol Source Type: research

ZEBs: Novel Players in Immune Cell Development and Function.
Abstract ZEB1 and ZEB2 are zinc-finger E homeobox-binding transcription factors best known for their role in driving epithelial to mesenchymal transition. However, in recent years our understanding of these two transcription factors has broadened, and it is now clear that they are expressed by a variety of immune cells of both myeloid and lymphoid lineages, including dendritic cells, macrophages, monocytes, B, T, and NK cells. In these cells, ZEBs function to regulate important transcriptional networks necessary for cell differentiation, maintenance, and function. Here, we review the current understanding of ZEB r...
Source: Trends in Immunology - April 4, 2019 Category: Allergy & Immunology Authors: Scott CL, Omilusik KD Tags: Trends Immunol Source Type: research

Recurrent Tonsillitis Tfh Cells Acquire a Killer Identity.
Abstract Group A Streptococcus (GAS) infection causes recurrent tonsillitis (RT) in some individuals. A recent study (Dan et al. Sci. Transl. Med. 2019;11:eaau3776) demonstrates that RT is associated with an impaired antibody response against a key streptococcal virulence factor. This factor, SpeA, can induce abnormal T follicular helper (Tfh) cells that are able to kill B cells. PMID: 30956068 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - April 4, 2019 Category: Allergy & Immunology Authors: Baessler A, Hale JS Tags: Trends Immunol Source Type: research

Immunotherapy in Hodgkin Lymphoma: The Road Ahead.
Abstract An extensive infiltrate of intratumoral immune cells is a hallmark of classic Hodgkin lymphoma (cHL) but these cells do result in an effective antitumor response. Immune checkpoint therapy, which activates 'exhausted' T cells, has been found to be highly effective in cHL, but responding patients commonly relapse. Combination approaches are currently being investigated but the assessment of benefit when adding immunotherapy is challenging. The pitfalls in designing combination studies derive from response endpoints that are difficult to measure, a lack of biomarkers that predict response, and a limited und...
Source: Trends in Immunology - April 1, 2019 Category: Allergy & Immunology Authors: Ansell SM Tags: Trends Immunol Source Type: research

Targeting Tumor-Associated Macrophages in Cancer.
Abstract Macrophages are phagocytes that serve as a first line of defense against pathogenic insults to tissues. These innate immune cells mount proinflammatory responses to pathogens and repair damaged tissues. However, tumor-associated macrophages (TAMs) express cytokines and chemokines that can suppress antitumor immunity and promote tumor progression. Preclinical studies have identified crucial pathways regulating the recruitment, polarization, and metabolism of TAMs during tumor progression. Moreover, novel therapeutics targeting these pathways can indirectly stimulate cytotoxic T cell activation and recruitm...
Source: Trends in Immunology - March 16, 2019 Category: Allergy & Immunology Authors: Pathria P, Louis TL, Varner JA Tags: Trends Immunol Source Type: research

To Sleep, Perchance to Survive?
Abstract Multicellular organisms exist in a sea of microbes. Survival is enabled by an immense diversity of antimicrobial peptides (AMPs) that maintain homeostasis with the microbiota. During pathogen infection, fruit fly survival varies directly with sleep. A newly-identified fruit fly sleep-regulator is also an AMP (Toda et al. Science 2019;363:509-515). Its characterization may clarify the association between sleep and surviving infection. PMID: 30885539 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - March 15, 2019 Category: Allergy & Immunology Authors: Ransohoff RM Tags: Trends Immunol Source Type: research

Elusive Neurotoxicity in T Cell-Boosting Anticancer Therapies.
Abstract Several T cell-boosting anticancer therapies (including anti-CD19 CAR-T cells and bi-specific T cell engagers, BiTEs) have been approved by the FDA for specific clinical indications. Their potency has been demonstrated in various clinical trials, but some life-threatening complications such as neurotoxicity remain poorly understood. Thus, by conducting multifaceted investigations, a better understanding of T cell immunotherapy-associated neurotoxicity to bridge the gap between basic research and clinical practice is urgently needed. PMID: 30876815 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - March 12, 2019 Category: Allergy & Immunology Authors: Zheng PP, Kros JM, Wang G Tags: Trends Immunol Source Type: research

The Cellular Immunotherapy Revolution: Arming the Immune System for Precision Therapy.
Abstract Immunotherapy treatments harnessing the patient's immune system herald a new era of personalized medicine, offering hope for curative responses in patients with serious illnesses. Cell-mediated immunity can eliminate cancer cells and provide durable remissions. This often relies on repurposing cytotoxic T cell activity through modified T cell receptors or chimeric antigen receptors. Furthermore, synthetic biology has expanded the cell engineering toolkit to provide immune cells with more functionality, including disease targeting, potency, and safety. We focus on T cell-based immunotherapy, highlighting d...
Source: Trends in Immunology - March 11, 2019 Category: Allergy & Immunology Authors: Paucek RD, Baltimore D, Li G Tags: Trends Immunol Source Type: research

Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy.
We present an updated exploratory analysis of how DNA methylation may define patient subgroups and can be targeted to develop tailored treatment combinations to help improve patient outcomes. PMID: 30853334 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - March 7, 2019 Category: Allergy & Immunology Authors: Emran AA, Chatterjee A, Rodger EJ, Tiffen JC, Gallagher SJ, Eccles MR, Hersey P Tags: Trends Immunol Source Type: research

Programming Isotype-Specific Plasma Cell Function.
Abstract Helper T cell induced plasma cells (PCs) that secrete class-switched neutralizing antibody are paramount to effective immunity. Following class-switch recombination (CSR), antigen-activated B cells differentiate into extrafollicular PCs or mature in germinal centers (GCs) to produce high-affinity memory B cells and follicular PCs. Many studies focus on the core transcriptional programs that drive central PC functions of longevity and antibody secretion. However, it is becoming clear that these central programs are further subdivided across antibody isotype with separable transcriptional trajectories. Dive...
Source: Trends in Immunology - March 4, 2019 Category: Allergy & Immunology Authors: Higgins BW, McHeyzer-Williams LJ, McHeyzer-Williams MG Tags: Trends Immunol Source Type: research

Priming Microglia for Innate Immune Memory in the Brain.
Abstract Microglia, the resident macrophages of the brain, are highly plastic and well known to be pre-activated or 'primed' by active inflammatory processes, resulting in amplified responses to a second inflammatory insult. Furthermore, the capacity of microglia to develop 'innate immune memory' (IIM), that is, long-lasting molecular reprogramming, has recently been demonstrated. Depending on the initial stimulus, IIM can either enhance or suppress microglial responses to a delayed, secondary insult. Moreover, both priming and IIM can affect pathological hallmarks of neurological disease in mouse models, which ma...
Source: Trends in Immunology - March 1, 2019 Category: Allergy & Immunology Authors: Neher JJ, Cunningham C Tags: Trends Immunol Source Type: research

T Cell-Redirecting Strategies to 'STAb' Tumors: Beyond CARs and Bispecific Antibodies.
Abstract The redirection of T cell activity towards cancer cells via targeting of tumor-associated antigens (TAAs) by soluble bispecific antibodies (bsAbs) or membrane-anchored chimeric antigen receptors is one of the most promising cancer immunotherapy strategies currently in development. We review here an emerging approach that combines aspects of antibody- and cell-based therapies: STAb immunotherapy, based on the endogenous secretion of T cell-redirecting bsAbs (STAb). STAb immunotherapies use ex vivo or in vivo genetic modifications of different cell types with nucleic acids or viral vectors encoding bsAbs; t...
Source: Trends in Immunology - March 1, 2019 Category: Allergy & Immunology Authors: Blanco B, Compte M, Lykkemark S, Sanz L, Alvarez-Vallina L Tags: Trends Immunol Source Type: research

Rethinking Thymic Tolerance: Lessons from Mice.
Abstract In the thymus, distinct cortex and medulla areas emphasize the division of labor in selection events shaping the αβT cell receptor repertoire. For example, MHC restriction via positive selection is a unique property of epithelial cells in the thymic cortex. Far less clear are the events controlling tolerance induction in the medulla. By acting in concert through multiple roles, including antigen production/presentation and chemokine-mediated control of migration, we propose that medullary epithelium and dendritic cells collectively enable the medulla to balance T cell production with negative s...
Source: Trends in Immunology - February 22, 2019 Category: Allergy & Immunology Authors: Inglesfield S, Cosway EJ, Jenkinson WE, Anderson G Tags: Trends Immunol Source Type: research