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Trends in Immunology

Andrew D Cook, Anne D Christensen, Damini Tewari, Stephen B McMahon, John A Hamilton
There is burgeoning interest in the interaction between the immune and nervous systems. Pain is mediated by primary sensory neurons (nociceptors) that can respond to a variety of thermal, mechanical and chemical signals. Cytokines are now recognized as important mediators of inflammatory pain. They can induce nociceptor sensitization indirectly via mediators, wherein neurons become primed and thus become more responsive to stimulation; alternatively, there is also evidence that cytokines can directly activate neurons via their specific receptors present on the neuronal cells...
January 12, 2018: Trends in Immunology
André Veillette, Jun Chen
Inhibitory immune checkpoint blockade has been one of the most significant advances in anticancer therapy of the past decade. Research so far has largely focused on improving adaptive immune functions, but recent studies have indicated that the signal-regulatory protein (SIRP)α-CD47 pathway, a phagocytosis checkpoint in macrophages and other innate immune cells, may be an interesting therapeutic target. Here, we summarize current knowledge about SIRPα-CD47 blockade, and highlight key issues for future investigations...
January 11, 2018: Trends in Immunology
Sara A Gibson, Etty N Benveniste
Although it has historically been studied in the context of cancer, recent literature has highlighted the importance of the highly conserved serine/threonine kinase casein kinase II (CK2) in inflammatory disorders. Most strikingly, CK2 is a major regulator of the Th17-Treg axis relevant to many T cell-driven autoimmune disorders including multiple sclerosis (MS).
January 4, 2018: Trends in Immunology
Kevin A Guttenplan, Shane A Liddelow
Macrophages and other immune cells are increasingly recognized to have unique and nontraditional functions in various tissues of the body. In a recent issue of Nature Medicine, Pirzgalska et al. [1] characterized a unique set of tissue-specialized macrophages that modulate the connection between the nervous system and subcutaneous fat.
December 28, 2017: Trends in Immunology
Shashi Gujar, Jonathan G Pol, Youra Kim, Patrick W Lee, Guido Kroemer
Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested...
December 20, 2017: Trends in Immunology
William Foulsham, Giulia Coco, Afsaneh Amouzegar, Sunil K Chauhan, Reza Dana
The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflammation at the cornea - blindness. Recent data have elucidated the contributions of specific anatomical components, immune cells, and soluble immunoregulatory factors in promoting homeostasis at the ocular surface...
December 13, 2017: Trends in Immunology
Laura K Mackay, Julia E Prier
Immune responses are often dissected at the molecular or cellular level, but rarely are they investigated at the scale of the whole organism. Here, Chevrier and colleagues reveal that an interconnected web of protective immunity exists between organs, which safeguards the host from systemic viral spread.
December 8, 2017: Trends in Immunology
Gérard Eberl, Thomas Pradeu
Theories are indispensable to organize immunological data into coherent, explanatory, and predictive frameworks. We propose to combine different models to develop a unifying theory of immunity which situates immunology in the wider context of physiology. We believe that the immune system will be increasingly understood as a central component of a network of partner physiological systems that interconnect to maintain homeostasis.
December 8, 2017: Trends in Immunology
Danyvid Olivares-Villagómez, Luc Van Kaer
Intestinal intraepithelial lymphocytes (IELs) are a large and diverse population of lymphoid cells that reside between the intestinal epithelial cells (IECs) that form the intestinal mucosal barrier. Although IEL biology has traditionally focused on T cells, recent studies have identified several subsets of T cell receptor (TCR)-negative IELs with intriguing properties. New insight into the development, homeostasis, and functions of distinct IEL subsets has recently been provided. Additional studies have revealed intricate interactions between different IEL subsets, reciprocal interactions between IELs and IECs, and communication of IELs with immune cells that reside outside the intestinal epithelium...
December 5, 2017: Trends in Immunology
Frank Siebenhaar, Frank A Redegeld, Stephan C Bischoff, Bernhard F Gibbs, Marcus Maurer
Mast cells (MCs) contribute to the pathogenesis of a multitude of diseases that include MC-driven disorders such as urticaria, type I allergies, and mastocytosis as well as autoimmune and other inflammatory disorders and malignant tumors. Here, we review and discuss the results of studies that identified and characterized how MCs contribute to disease and, importantly, what strategies may be used to target MCs and MC effects therapeutically. Specifically, we discuss the most common approaches for investigating the role and relevance of MCs in various diseases...
November 28, 2017: Trends in Immunology
Teneema Kuriakose, Thirumala-Devi Kanneganti
Z-DNA-binding protein 1 (ZBP1), initially reported as an interferon (IFN)-inducible tumor-associated protein, harbors nucleic acid-binding domains for left-handed helix (Z-form) and receptor-interacting protein homotypic interaction motif (RHIM) domains for protein homotypic interactions. Recent studies have identified ZBP1 as an innate sensor of viral infections and a target of viral evasion strategies, regulating cell death, inflammasome activation, and proinflammatory responses. ZBP1 also functions during development and can trigger perinatal lethality when its RHIM-dependent interactions are not restricted...
November 24, 2017: Trends in Immunology
Pedro M Rodrigues, Pärt Peterson, Nuno L Alves
Medullary thymic epithelial cells (mTECs) play a central role in T cell tolerance. However, how the mTEC compartment is maintained remains elusive. We review recent discoveries on new transcription factors involved in mTEC homeostasis and discuss the possibility that their actions might be facilitated by the unique biology of mTECs.
November 24, 2017: Trends in Immunology
Jessica N Lancaster, Yu Li, Lauren I R Ehrlich
As they differentiate, thymocytes encounter spatially restricted cues critical for differentiation and selection of a functional, self-tolerant T cell repertoire. Sequential migration of developing T cells through distinct thymic microenvironments is enforced by the ordered expression of chemokine receptors. Herein, we provide an updated perspective on T cell differentiation through the lens of recent advances that illuminate the dynamics of chemokine-driven thymocyte migration, localization, and interactions with stromal cells...
November 18, 2017: Trends in Immunology
Frode L Jahnsen, Espen S Bækkevold, Johannes R Hov, Ole J Landsverk
Disruptions to the gut microbiota have been associated with a variety of diseases. Understanding the underlying mechanisms that regulate the maintenance of a healthy microbiota may therefore have therapeutic implications. Secretory IgA play a unique role in immune-microbiota crosstalk by directly binding to bacteria in the gut lumen. Microbe-specific IgA responses co-develop with the assembly of the gut microbiota during infancy, and resemble those of adults by 2 years postnatally in the healthy host. We propose here that microbiota-specific IgA-producing gut plasma cells generated during infancy live for many decades and contribute to a stable microbiota community...
November 18, 2017: Trends in Immunology
Michelle L Bookstaver, Shannon J Tsai, Jonathan S Bromberg, Christopher M Jewell
Polymers, lipids, scaffolds, microneedles, and other biomaterials are rapidly emerging as technologies to improve the efficacy of vaccines against infectious disease and immunotherapies for cancer, autoimmunity, and transplantation. New studies are also providing insight into the interactions between these materials and the immune system. This insight can be exploited for more efficient design of vaccines and immunotherapies. Here, we describe recent advances made possible through the unique features of biomaterials, as well as the important questions for further study...
November 15, 2017: Trends in Immunology
Jakob von Moltke, Marion Pepper
Type 2 immune responses have evolved to sense and respond to large, non-replicating infections or non-microbial noxious compounds in tissues. The development of these responses therefore depends upon highly coordinated and tightly regulated tissue-residing cellular sensors and responders. Multiple exposure to type 2 helper T cell (Th2)-inducing stimuli further enhances both the diversity and potency of the response. This review discusses advances in our understanding of the interacting cellular subsets that comprise both primary and secondary type 2 responses...
November 6, 2017: Trends in Immunology
Chunyan Gu-Trantien, Karen Willard-Gallo
T follicular helper (TFH) cells are characteristically defined by their CXCR5 positivity and homing to B cell follicles in secondary lymphoid organs (SLO). An expanded subpopulation of functionally comparable and phenotypically similar PD-1(hi)CXCR5(-)CD4(+) T cells were recently identified in breast cancer (BC) and rheumatoid arthritis (RA) to have beneficial or detrimental roles, respectively, but are they inflammatory tissue effector TFH cells?
October 27, 2017: Trends in Immunology
Angelika S Rambold, Erika L Pearce
Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism...
January 2018: Trends in Immunology
Mohan S Maddur, Srini V Kaveri, Jagadeesh Bayry
Intravenous immunoglobulin (IVIG), a pooled normal IgG formulation prepared from thousands of healthy donors' plasma, is extensively used for the immunotherapy of autoimmune and inflammatory disorders. Recent reports demonstrate that IVIG exerts anti-inflammatory actions by stimulating the activation and expansion of regulatory T (Treg) cells by multiple mechanisms via antigen-presenting cells (APCs).
November 2017: Trends in Immunology
Courtney A Iberg, Andrew Jones, Daniel Hawiger
Mechanisms of tolerance initiated in the thymus are indispensable for establishing immune homeostasis, but they may not be sufficient to prevent tissue-specific autoimmune diseases. In the periphery, dendritic cells (DCs) play a crucial tolerogenic role, extending the maintenance of immune homeostasis and blocking autoimmune responses. We review here these essential roles of DCs in orchestrating mechanisms of peripheral T cell tolerance as determined by targeted delivery of defined antigens to DCs in vivo in combination with various genetic modifications of DCs...
November 2017: Trends in Immunology
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