1,721,100 research outputs found
Writer's block: preventing m(6)A mRNA methylation promotes T cell naivety
No full text(c) 2017 Australasian Society for Immunology Inc. All rights reserved011sciescopu
Self-gratification yields not-so-naïve T cells
No full textNaive T cells differentiate into memory subsets upon exposure to their cognate foreign antigen. However, before such encounters, some naive T cells are ‘imprinted’ through their interactions with self targets.1221sciescopu
Beyond Hygiene: Commensal Microbiota and Allergic Diseases.
No full textComplex communities of microorganisms, termed commensal microbiota, inhabit mucosal surfaces and profoundly influence host physiology as well as occurrence of allergic diseases. Perturbing factors such as the mode of delivery, dietary fibers and antibiotics can influence allergic diseases by altering commensal microbiota in affected tissues as well as in intestine. Here, we review current findings on the relationship between commensal microbiota and allergic diseases, and discuss the underlying mechanisms that contribute to the regulation of allergic responses by commensal microbiota.2
Blowing on embers: commensal microbiota and our immune system
Full text linkVertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens.open112934sciescopu
Induction of Immune Tolerance to Dietary Antigens
No full textThe intestinal immune system is continuously exposed to massive amounts of diverse antigens derived from both food and intestinal microbes. Immunological tolerance to these enteric antigens is critical for ensuring intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by the exposure of antigen via the oral route, emphasizing the role of intestinal immune system for preventing unnecessary hypersensitivity reactions to innocuous dietary and microbial antigens. Here, we discuss how dietary antigens are recognized by intestinal immune systems and highlight the role of Foxp3(+) regulatory CD4(+) T cells (Tregs) in establishment of oral tolerance, the tolerogenic features of intestinal dendritic cells that induce development of Foxp3(+) Tregs, and the factors that promote development of the intestinal dendritic cells.1187sciescopu
The aged lymphoid tissue environment fails to support naive T cell homeostasis
Full text linkAging is associated with a gradual loss of naive T cells and a reciprocal increase in the proportion of memory T cells. While reduced thymic output is important, age-dependent changes in factors supporting naive T cells homeostasis may also be involved. Indeed, we noted a dramatic decrease in the ability of aged mice to support survival and homeostatic proliferation of naive T cells. The defect was not due to a reduction in IL-7 expression, but from a combination of changes in the secondary lymphoid environment that impaired naive T cell entry and access to key survival factors. We observed an age-related shift in the expression of homing chemokines and structural deterioration of the stromal network in T cell zones. Treatment with IL-7/mAb complexes can restore naive T cell homeostatic proliferation in aged mice. Our data suggests that homeostatic mechanisms that support the naive T cell pool deteriorate with age
© The Author(s) 2016111101sciescopu
Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine
No full textCD4 T cells differentiate into ROR gamma t/IL-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naive precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naive CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset. C.The Korean Society for Molecular and Cellular Biology. All rights reserved
Self-recognition sensitizes mouse and human regulatory T Cells to low-dose CD28 superagonist stimulation
Full text linkIn rodents, low doses of CD28-specific superagonistic monoclonal antibodies (CD28 superagonists, CD28SA) selectively activate regulatory T cells (Treg). This observation has recently been extended to humans, suggesting an option for the treatment of autoimmune and inflammatory diseases. However, a mechanistic explanation for this phenomenon is still lacking. Given that CD28SA amplify T cell receptor (TCR) signals, we tested the hypothesis that the weak tonic TCR signals received by conventional CD4+ T cells (Tconv) in the absence of cognate antigen require more CD28 signaling input for full activation than the stronger TCR signals received by self-reactive Treg. We report that in vitro, the response of mouse Treg and Tconv to CD28SA strongly depends on MHC class II expression by antigen-presenting cells. To separate the effect of tonic TCR signals from self-peptide recognition, we compared the response of wild-type Treg and Tconv to low and high CD28SA doses upon transfer into wild-type or H-2M knockout mice, which lack a self-peptide repertoire. We found that the superior response of Treg to low CD28SA doses was lost in the absence of self-peptide presentation. We also tested if potentially pathogenic autoreactive Tconv would benefit from self-recognition-induced sensitivity to CD28SA stimulation by transferring TCR transgenic OVA-specific Tconv into OVA-expressing mice and found that low-dose CD28SA application inhibited, rather than supported, their expansion, presumably due to the massive concomitant activation of Treg. Finally, we report that also in the in vitro response of human peripheral blood mononuclear cells to CD28SA, HLA II blockade interferes with the expansion of Treg by low-dose CD28SA stimulation. These results provide a rational basis for the further development of low-dose CD28SA therapy for the improvement of Treg activity. © 2018 Langenhorst, Tabares, Gulde, Becklund, Berr, Surh, Beyersdorf and Hünig101sciescopu
Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lungthe lung
No full textImmune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung. As with the intestine, we found that the absence TRAF6 expression by DCs led to spontaneous generation of Th2-associated immune responses and increased susceptibility to model antigen-induced asthma. To examine the role of commensal microbiota mice deficient in TRAF6 in DCs were treated with broad-spectrum antibiotics and/or re-derived on a germ-free (GF) background. Interestingly, we found that antibiotics-treated specific pathogen-free (SPF), but not GF, mice showed restored immune tolerance in the absence of DC-expressed TRAF6. We further found that antibiotics mediate microbiota-independent effects on lung T cells to promote immune tolerance in the lung. This work provides both a novel tool for studying immune tolerance in the lung, and an advance in our conceptual understanding of potentially common molecular mechanisms of immune tolerance in both the intestine and the lung.
© The Author 2017. Published by Oxford University Press on behalf
of The Japanese Society for Immunology.111sciescopu
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