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Knockout CD45 in LatY136F mice affact T cell activation

ABSTRACT: Background: The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mice with a mutation at the LAT-PLCγ1 binding site (Y136) have a defect in thymocyte development due to dampened TCR signaling. CD4 + T cells that do reach the periphery are hyper-activated and skewed to Th2. Over time, these mice develop an autoimmune-like syndrome, characterize by overproduction of Th2 cytokines, T cell infiltration into various organs, and B cell activation, isotype switching, and autoantibody production. In this study, we established LatY136F and LatY136F-CD45 KO mice and using them to investigate to role of CD45 in TCR signalling via flow cytometry and scRNA sequencing. Conclusion: Knockout CD45 in LatY136F mice affact T cell activation

ORGANISM(S): Mus musculus

PROVIDER: GSE273821 | GEO | 2025/08/01

REPOSITORIES: GEO

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Single-cell RNA-seq analysis of the lymphoproliferative disorders triggered by defective LAT signalosome. Modulation of the pathology in the context of two additional mutations, Stat6KO or Grap2KO

Project description:LatY136F mice in which tyrosine 136 of the LAT adaptor is mutate accumulate CD4+ T cells that trigger a fast-onset autoimmune and inflammatory condition called LAT signaling pathology (LSP). Its histopathological manifestations resemble those of human IgG4-related disease (IgG4-RD), an inflammatory condition unifying a constellation of clinical entities leading to multi-organ damage. LatY136F mice deprived of STAT6 transcription factor develop a lymphoproliferative disorder with a kinetics and magnitude identical to that of LatY136F mice. Consistent with a role of STAT6 in Th2 differentiation, the LatY136F x Stat6KO lymphoproliferative disorder is characterize by a lymphoproliferation of both CD4 and CD8 Tc producing high levels of IFN-g. This Tc proliferation is associated with massive B cell proliferation and hyperglobulinemia G2a and G2b. Using single-cell RNA sequencing, we analyzed 48287 CD4 and CD8 T cells isolated from the spleen of LatY136F and LatY136F x Stat6KO mice over the period that leads to LSP installation. In this study, LatY136F lymphoproliferative disorder is also analyze in Grab2KO mice. Unexpectedly, LatY136F x Grap2KO mice present a lymphoproliferative disorder similar to the one observed in LatY136F mice but this time TCRgd Tc.

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Knockout CD45 in LatY136F mice affact T cell activation

Project description:Knockout CD45 in LatY136F mice affact T cell activation

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Single-cell RNA-seq analysis of the T-cell lymphoproliferative and inflammatory disorders triggered by defective LAT signalosome

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