Vγ6+ γδ T cells play a critical role in protection against infection by Escherichia coli
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PROVIDER: PRJNA604204 | ENA |
REPOSITORIES: ENA
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Project description:γδ T cells producing interleukin 17A (IL-17A), which are mainly Vγ4 and Vγ6 subsets, are involved in protection against infection by extracellular bacteria. Using a new Vγ6-specific monoclonal antibody (mAb) (1C10-1F7) which we recently developed, we found that IL-17A+ Vγ6+ γδ T cells increased predominantly in the peritoneal cavity compared with IL-17A+ Vγ4+ γδ T cells during intraperitoneal Escherichia coli infection. The number of IL-17A+ Vγ6+ γδ T cells, which rapidly became CD69+ from CD69-, peaked at 12 h after infection. In vivo treatment with 1C10-1F7 mAb significantly inhibited the accumulation of neutrophils and hampered the resolution of E. coli infection. These results suggest that rapid activation of IL-17A+ Vγ6+ γδ T cells contributed to host defence against E. coli infection.
2020-02-28 | GSE144617 | 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:We recently found that a unique subset of innate-like γδ T cells develop from the DN2a-stage of the fetal thymus independent of the zinc-finger transcription factor B-cell leukemia/lymphoma 11b (Bcl11b). Herein we characterized these Bcl11b-independent γδ T cells in the periphery as CD5−NK1.1+ and Granzyme B+, and show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca2+ influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues such as the liver. Bcl11b-independent CD5−NK1.1+ γδ T cells appeared and contributed to early protection before Bcl11b-dependent CD5+NK1.1− γδT cells following Listeria monocytogenes infection, recapitulating their appearance during thymic development.
2017-10-11 | GSE89906 | GEO
Project description:One common way to classify functional γδ T cell subsets is based on the expressed variable gene region of the T-cell-receptor (TCR) γ-chain. It is established that the TCRs of murine IL-17 producing γδ T cells are either Vγ6+ or Vγ4+. The majority of IL-17 producers get functionally pre-programmed in the prenatal thymus, and persist thereafter as tissue-resident cells into adulthood. Little is known about the role of the expressed TCR on IL-17 effector fate acquisition, and if also other subsets can produce IL-17 under certain circumstances. To address this question, we took advantage of a mouse model that lack the Vγ4 and Vγ6 γ-chain (Vγ4-/- / Vγ6-/- double knock-out). Initial results indicate that Vγ1+ T cells show increased IL-17 production capability in the absence of Vγ4+ and Vγ6+ γδ T cells, suggesting that the γδTCR does not always instruct the phenotype. This raises the question about the ontogenetic origin, which might be a TCR-independent default mechanism to instruct IL-17 production by γδ T cells, of IL-17+ Vγ1+ T cells. Moreover, it remains elusive if these Vγ1+ T cells (i) adopt highly similar tissue-specific gene expression programs and (ii) functionality in health and disease, than the Vγ4+ and Vγ6+ T cells.
2025-09-24 | GSE284198 | GEO
Project description:One common way to classify functional γδ T cell subsets is based on the expressed variable gene region of the T-cell-receptor (TCR) γ-chain. It is established that the TCRs of murine IL-17 producing γδ T cells are either Vγ6+ or Vγ4+. The majority of IL-17 producers get functionally pre-programmed in the prenatal thymus, and persist thereafter as tissue-resident cells into adulthood. Little is known about the role of the expressed TCR on IL-17 effector fate acquisition, and if also other subsets can produce IL-17 under certain circumstances. To address this question, we took advantage of a mouse model that lack the Vγ4 and Vγ6 γ-chain (Vγ4-/- / Vγ6-/- double knock-out). Initial results indicate that Vγ1+ T cells show increased IL-17 production capability in the absence of Vγ4+ and Vγ6+ γδ T cells, suggesting that the γδTCR does not always instruct the phenotype. This raises the question about the ontogenetic origin, which might be a TCR-independent default mechanism to instruct IL-17 production by γδ T cells, of IL-17+ Vγ1+ T cells. Moreover, it remains elusive if these Vγ1+ T cells (i) adopt highly similar tissue-specific gene expression programs and (ii) functionality in health and disease, than the Vγ4+ and Vγ6+ T cells.
2025-09-24 | GSE284167 | GEO
Project description:Dermal fibroblasts play a central role in skin model protection against C. albicans invasion
| PRJNA343010 | ENA
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:Organismal ageing is associated with loss of immune function and higher incidence of cancer. Whether the γδ T cell pool changes upon organismal ageing is not known. In this study we have characterized γδ T cells in peripheral lymph nodes from old and young mice. We found that the γδ T cell pool is severely altered in old mice. The IL-17 producing γδ lineage becomes dominating while IFN-γ producing γδ1 T cells are declining. γδTCR sequencing revealed no collapse in diversity but oligoclonal expansions in Vγ4 γδ17 subsets. Pro-tumourigenic invariant Vγ6 cells are present only in aged lymph nodes, represent the majority of γδ T cells in the tumour, and are associated with faster tumour progression.
2019-05-22 | E-MTAB-7178 | biostudies-arrayexpress
Project description:The early-life period is increasingly being recognized as a window of opportunity to shape immunity where microbiota and related probiotics have an important impact. Innate γδ T cells are the first T cells generated in utero populating epithelial tissues such as the lung contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate γδ T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth the murine lung T cell population was specifically dominated by IL17-committed γδ T cells expressing an invariant Vγ6Vδ1 TCR. Single-cell-RNA-sequencing showed that the biased IL17-commitment of perinatal lung γδT cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung Vγ6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus(L.rhm.), but not of Bifidobacterium animalis subsp.lactis(B.lac.), increased significantly their frequency resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed γδT cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process.
2025-09-16 | GSE278178 | GEO
Project description:Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
2023-07-20 | PXD039463 | Pride