Got my γδ17 T cells to keep me warm

© 2018 Nature America Inc., part of Springer Nature. All rights reservedγδ T cells accumulate with age in adipose tissue and produce the cytokine IL-17, which controls the homeostasis of regulatory T cells and adaptive thermogenesis. Thus, maintenance of core body temperature unexpectedly relies on these adipose tissue–resident γδ17 T cells.info:eu-repo/semantics/publishedVersio

Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner.

Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ T cell-sufficient dams. Upon helminth infection, mice born from TCRδ-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ-/- dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ T cell-microbiota-SCFA axis regulating neonatal lung immunity

Crosstalk between γδ T cells and the microbiota.

From PubMed via Jisc Publications RouterHistory: received 2021-01-20, accepted 2021-07-07Publication status: aheadofprintFunder: European Molecular Biology Organization (EMBO); Grant(s): LTF 191-2019Funder: "la Caixa" Foundation (Caixa Foundation); Grant(s): LCF/PR/HR19/52160011Funder: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation); Grant(s): PZ00P3_185880The role of the microbiota in the development and function of γδ T cells-a T cell subset characterized by a T cell receptor composed of one γ-chain and one δ-chain-has been investigated in multiple organs in mice and humans. Interactions between the microbiota and γδ T cells affect both tissue homeostasis and disease pathologies. Notably, microbiota-induced interleukin-17 (IL-17)-producing-γδ T cells can mediate a range of immunological processes, from metabolic disorders to neuroinflammation via the gut-brain axis. However, the bidirectional interactions between γδ T cells and the microbiota have not been fully determined. In this Perspective, we dissect the roles of microbiota in modulating γδ T cell development and function, and evaluate the evidence for γδ T cell selection of commensal communities. We also discuss the potential implications of these cells in health and disease and the major open questions and research avenues in the field. [Abstract copyright: © 2021. Springer Nature Limited.

IL-17+ γδ T cells as kick-starters of inflammation

Copyright © 2017, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.Shortly after the discovery of interleukin 17 (IL-17)-producing CD4+ helper T cells (TH17 cells), it was found that γδ T cells can also secrete large amounts of this pro-inflammatory cytokine. A decade later, it is now known that IL-17+ γδ T cells (γδ17 T cells) are often the main providers of IL-17A in various models of inflammatory diseases, while they also contribute to protective immune responses to infectious organisms. Due to an intricate thymic program of differentiation, γδ17 T cells are able to respond faster than TH17 cells do and thus predominate in the early stages of inflammatory responses. Here we review the current knowledge of the development, activation and pathophysiological functions of γδ17 T cells, aiming to increase the awareness in the community of the therapeutic potential of this 'other side' of IL-17-mediated immune responses.Supported by the European Research Council (CoG_646701 to B.S.-S.) and Fundação para a Ciência e Tecnologia (PD/BD/105855/2014 to P.H.P.; IF/00013/2014 to J.C.R.).info:eu-repo/semantics/publishedVersio

MicroRNA-146a controls IFN-g production and functional plasticity of murine gd T cells by targeting Nod1

γδ T cells have emerged as key providers of the proinflammatory cytokines interleukin 17 (IL-17) and interferon-γ (IFN-γ) in various models of infection, inflammation, and autoimmunity. Our previous epigenetic and transcriptional analyses have shown that whereas CD27+ γδ T cells are committed to IFN-γ expression, the IL-17 producing CD27- subset has limited plasticity to co-express both cytokines under inflammatory conditions (Schmolka et al. Nat Immunol 2013). To further understand the molecular control of this plasticity we now investigated the potential role of microRNA (miRNA)-mediated post-transcriptional regulation.info:eu-repo/semantics/publishedVersio

The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration

The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin IL-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of IFNγ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFNγ. Neutrophil-depletion experiments, which dramatically reduce lung injury, revealed that neutrophils are primarily responsible for the IL-17A-dependent release of IL-33 into the airways. Taken together, our results reveal an IL-17A-neutrophil-axis that can drive IL-33 during helminth infection, highlighting an additional pathway by which IL-17A regulates pulmonary type 2 immunity.</p

MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1

γδ T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27-) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- T cells in vitro and in vivo. On the basis of biochemical purification of Argonaute 2-bound miR-146a targets, we identified Nod1 to be a relevant mRNA target that regulates γδ T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17+ IFN-γ+ γδ27- cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.info:eu-repo/semantics/publishedVersio