Similar Datasets
Project description:γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (Treg) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF+ γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα+ and Pdpn+ stromal-cell production of IL-33 in adipose tissue. Mice lacking γδ T cells or IL-17A exhibited decreases in both ST2+ Treg cells and IL-33 abundance in visceral adipose tissue. Remarkably, these mice also lacked the ability to regulate core body temperature at thermoneutrality and after cold challenge. Together, these findings uncover important physiological roles for resident γδ T cells in adipose tissue immune homeostasis and body-temperature control.
| S-EPMC8299914 | biostudies-literature
Project description:The conventional notion of “immune privilege” of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology (Louveau, Trends Immunol 2015; Kipnis science 2016; Filiano, Nat Rev Neurosciences 2017). Surprisingly, such neuroimmune functions have been linked to “pro-inflammatory” cytokines like IL-4 or IFN-α, shown to control behavioural and social cognition (Derecki, JEM 2010; Filiano, Nature 2016). Here we identify a pro-cognitive role for IL-17 in short-term memory that derives from a previously unknown meningeal-resident γδ T cell subset. This was mostly composed of foetal thymic-derived Vγ6+ T cells, found in the meninges at birth and persisting throughout life, where they were strikingly polarized towards IL-17 production. In fact, γδ T cells were the overwhelming source of meningeal IL-17, whereas IFN-γ was mostly provided by T cells. To assess whether the constitutive production of IL-17 by γδ T cells influenced the cognitive performance of mice, we tested TCRδ-/-, IL-17-/- and respective WT littermate control mice in classical learning paradigms. We observed that mice deficient either for γδ T cells or IL-17 displayed impaired short-term memory in the Y maze paradigm, while retaining normal long-term spatial memory in the Morris water maze. A detailed proteomics analysis of the hippocampus provided mechanistic insight into reduced plasticity of the glutamatergic synapses in the absence of IL-17, which associated with impaired Long Term Potentiation (LTP). Conversely, IL-17 enhanced glial cell production of Brain Derived Neurotropic Factor (BDNF), whose exogenous provision rescued the LTP defect of IL-17-/- animals. Altogether, our data demonstrate that foetal-derived γδ T cells populate the brain meninges where they regulate synaptic plasticity and short-term memory through a non-inflammatory IL-17-dependent mechanism.
2019-10-16 | PXD007574 | Pride
Project description:Psoriasis is a chronic immune-mediated skin condition influenced by genetics and environmental factors. γδ T cells, as the main sources of IL-17A, play pivotal roles in the inflammatory processes of psoriasis. During psoriasis pathogenesis, inhibiting the secretion of IL-17A has emerged as a novel therapeutic approach for treating psoriasis. Double-negative T (DNT) cells is a novel type of immunosuppressive cells. Our preliminary research has unveiled that DNT cells play a significant immunoregulatory role in autoimmune and allergic diseases. In this study, we aimed to evaluate the protection of DNT cells and explore its underlying mechanism.
2024-04-10 | GSE248626 | GEO
Project description:RNA sequencing of PLZF+ and PLZF- γδ T cell subsets from the spleen, inguinal lymph nodes, lungs and adipose tissue for gene expression analysis
2020-08-25 | GSE156782 | GEO
Project description:TCR γ chain loci of mice have seven variable (Vγ) gene segments (Vγ1, Vγ2, Vγ3, Vγ4, Vγ5, Vγ6, and Vγ7) using the Heilig and Tonegawa nomenclature. Vγ6+ γδ T cells, which develop in the thymus at the perinatal stage, are distributed within the mucosal tissues in the periphery. Vγ6+ γδ T cells are exclusive interleukin (IL)-17 producers among γδ T cells, and Vγ6+ IL-17A+ γδ T (γδT17) cells play important roles in protection against microbial infection and in the pathogenesis of inflammatory diseases, such as colitis and autoimmune diseases. We have previously reported that γδT17 cells develop from the CD4–CD8– (DN)2b stage in the thymus at the prenatal stage in a Bcl11b-dependent manner. However, details of the development of Vγ6+ γδT17 cells remain obscure. To analyze Vγ6+ γδ T cells in detail, we recently developed a monoclonal antibody (mAb; termed 1C10-1F7) specific to mouse Vg6 chain. Use of this mAb revealed that Vγ6+ γδ T cells in 0-day-old thymus were co-localized with medullary thymic epithelial cells (mTECs), which regulate T cell tolerance by self-antigen presentation using major histocompatibility complex (MHC) class II. Here, we report that MHC class II in the thymus inhibits the generation of Vγ6+ γδT17 cells.
2022-08-01 | GSE180320 | GEO
Project description:Reduced TCRγδ signal strength manifest by constrained Syk activity engages PI3K to maintain expression of key master regulators of the IL-17 program; RORγt and c-Maf, and drive thymic development of IL-17A-secreting γδ T cells (γδ17 cells). Notably, inhibition of PI3K not only abrogates γδ17 cell development, but also permits γδ progenitors to adopt a type-I interferon gene expression signature that identifies a novel CD8(+)Sca-1(+) γδ T cell subset.
2021-07-05 | GSE167943 | GEO
Project description:Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but how they contribute to disorders such as SpA is still unclear. Here we describe the presence of particular RORγt+T-betloPLZF- iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt+ iNKT and γδ-hi T cells showed profound IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed a unique Th17 skewed phenotype and gene expression profile. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, these findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.
2018-11-17 | GSE122624 | GEO
Project description:γδ T cells producing interleukin-17A (γδT17) are thought to develop spontaneously in the thymus and to be maintained in the periphery. Previous studies suggested a role for T-helper 17 (Th17) cells in the maintenance of γδT17 via the expression of transforming growth factor-β1 (TGFβ1). However, we have previously found that Th17 cells were not required for expansion of γδT17 cells after lung transplant in a mouse model. Using mice deficient in signal transducer and activator of transcription 3 (STAT3) in CD4+ T cells, which are unable to develop Th17 cells, we investigated the requirement for Th17 cells and TGFβ1 to maintain γδT17 cells in the lung and lymphoid tissues. At steady state, we found no defect in γδT17 cells in the thymus or periphery of these mice. Further, STAT3-deficient CD4+ T cells produced significantly higher levels of TGFβ1 than wild-type CD4+ T cells under Th17 differentiation conditions in vitro. To determine whether STAT3-deficient CD4+ T cells could expand γδT17 cells in vivo, we used TCRβ-/- mice, which are known to have a defect in γδT17 cells that can be rescued by Th17 cells. However, adoptive transfer of wild-type Th17 cells or bulk CD4+ T cells did not expand γδT17 cells in TCRβ-/- mice. In contrast, interferon-γ+ γδ T cells preferentially expanded, particularly in the lungs. Interestingly, we found in vivo and in vitro that TGFβ1 may negatively regulate the pool of γδT17 cells. Our data suggest that Th17 cells and TGFβ1 are not required for the maintenance of γδT17 cells.
| S-EPMC5360492 | biostudies-literature
Project description:Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.
| S-EPMC5953325 | biostudies-literature
Project description:IL-17A-producing γδ T cells in mice consist primarily of Vγ6+ tissue-resident cells and Vγ4+ circulating cells. How these γδ T cell subsets are regulated during homeostasis and cancer remains poorly understood. Using single-cell RNA sequencing and flow cytommetry, we show that lung Vγ4+ and Vγ6+ cells from tumor-free and tumor-bearing mice express contrasting cell surface molecules as well as distinct co-inhibitory molecules, which function to suppress their expansion. Vγ6+ cells express constitutively high levels of PD-1, whereas Vγ4+ cells upregulate TIM-3 in response to tumor-derived IL-1β and IL-23. Inhibition of either PD-1 or TIM-3 in mammary tumor-bearing mice increased Vγ6+ and Vγ4+ cell numbers, respectively. We found that genetic deletion of γδ T cells elicits responsiveness to anti-PD-1 and anti-TIM-3 immunotherapy in a mammary tumor model that is refractory to T cell checkpoint inhibitors, indicating that IL-17A-producing γδ T cells instigate resistance to immunotherapy. Together, these data demonstrate how lung IL-17A-producing γδ T cell subsets are differentially controlled by PD-1 and TIM-3 in steady-state and cancer.
| S-EPMC9732671 | biostudies-literature