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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
Francesca Levi-Schaffer, Ofer Mandelboim
Coactivating and inhibitory receptors that share at least one ligand interact with a wide variety of ligands, indicating their importance in a range of situations. Here, we discuss principles of mainly human paired receptor function and ligand recognition, and possible therapeutic implications of targeting these receptors in cancer, autoimmune diseases, and allergy. We summarise and emphasise the idea that these receptors, which have evolved in part in response to pathogen pressure, fine-tune the immune response, preserve homeostasis, and that pathogens and tumours use the dominance of the inhibitory receptors over the coactivating receptors to avoid immune elimination...
October 20, 2017: Trends in Immunology
Matthew R Hepworth
Innate lymphoid cells (ILCs) play critical roles in immune homeostasis and immunity to pathogens. Increasing evidence implicates dysregulated ILC responses as drivers of disease pathogenesis in multiple inflammatory disorders. A recent study reveals how inflammatory ILC responses can be suppressed by a newly defined subset of ILCs with regulatory function.
October 10, 2017: Trends in Immunology
David D Lo
Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues...
September 22, 2017: Trends in Immunology
Pilar López-Cotarelo, Carolina Gómez-Moreira, Olga Criado-García, Lucas Sánchez, José Luis Rodríguez-Fernández
The word chemokine is a combination of the words chemotactic and cytokine, in other words cytokines that promote chemotaxis. Hence, the term chemokine receptor refers largely to the ability to regulate chemoattraction. However, these receptors can modulate additional leukocyte functions, as exemplified by the case of CCR7 which, apart from chemotaxis, regulates survival, migratory speed, endocytosis, differentiation and cytoarchitecture. We present evidence highlighting that multifunctionality is a common feature of chemokine receptors...
September 18, 2017: Trends in Immunology
Walter K Mowel, Jonathan J Kotzin, Sam J McCright, Vanessa D Neal, Jorge Henao-Mejia
The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues...
September 14, 2017: 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).
September 12, 2017: Trends in Immunology
Wing Y Lam, Deepta Bhattacharya
Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy...
September 11, 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...
September 8, 2017: Trends in Immunology
Niki M Moutsopoulos, Joanne E Konkel
The oral mucosal barrier is constantly exposed to a plethora of triggers requiring immune control, including a diverse commensal microbiome, ongoing damage from mastication, and dietary and airborne antigens. However, how these tissue-specific cues participate in the training of immune responsiveness at this site is minimally understood. Moreover, the mechanisms mediating homeostatic immunity at this interface are not yet fully defined. Here we present basic aspects of the oral mucosal barrier and discuss local cues that may modulate and train local immune responsiveness...
September 8, 2017: Trends in Immunology
Stephen M Hedrick
As we describe the immune system in ever more exquisite detail, we might find that no matter how successful, this approach will not be sufficient to understand the spread of infectious agents, their susceptibility to vaccine therapy, and human disease resistance. Compared with the strict reductionism practiced as a means of characterizing most biological processes, I propose that the progression and outcome of disease-causing host-parasite interactions will be more clearly understood through a focus on disease ecology...
September 4, 2017: Trends in Immunology
Carole Henry, Anna-Karin E Palm, Florian Krammer, Patrick C Wilson
Antibody responses are essential for protection against influenza virus infection. Humans are exposed to a multitude of influenza viruses throughout their lifetime and it is clear that immune history influences the magnitude and quality of the antibody response. The 'original antigenic sin' concept refers to the impact of the first influenza virus variant encounter on lifelong immunity. Although this model has been challenged since its discovery, past exposure, and likely one's first exposure, clearly affects the epitopes targeted in subsequent responses...
August 31, 2017: Trends in Immunology
Mari Regoli, Eugenio Bertelli, Massimo Gulisano, Claudio Nicoletti
Intestinal macrophages expressing the fraktalkine receptor (CX3CR1(+)) represent a cell population that plays a variety of roles ranging from maintaining intestinal immune homeostasis at steady state to controlling antigen access by extending transepithelial dendrites (TEDs) to capture luminal microbes and shuttle them across the epithelium to initiate immune responses. However, recent evidence shows that very early during infection, pathogen-capturing CX3CR1(+) macrophages migrate to the lumen of the small intestine, therefore preventing pathogens from traversing the epithelium...
August 24, 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
Julien Zuber, Megan Sykes
Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells...
November 2017: Trends in Immunology
Darienne R Myers, Julie Zikherman, Jeroen P Roose
Since the 1990s it has been known that B and T lymphocytes exhibit low-level, constitutive signaling in the basal state (tonic signaling). These lymphocytes display a range of affinity for self, which in turn generates a range of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling...
November 2017: Trends in Immunology
Thomas Simon, Jonathan S Bromberg
Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system...
November 2017: Trends in Immunology
Jacques Deguine
No abstract text is available yet for this article.
October 2017: Trends in Immunology
Stefania Gallucci, Massimo E Maffei
From plants to mammals, pattern recognition receptors (PRRs) specifically recognize DNA, as a potential marker of either infection or damage. These receptors play critical roles in inflammation, immunity, and pathogen resistance. Importantly, given the ubiquity of DNA, its sensing must be tightly regulated. DNA localization plays a key role in recognition, as highlighted by Toll-like receptor 9 (TLR9) in the endosomal compartment and cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) in the cytoplasm...
October 2017: Trends in Immunology
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