QRICH1 is a negative regulator of T cell activation via the CARD11 signalosome
نویسندگان
چکیده
Abstract Controlled lymphocyte activation is crucial for defending against pathogens while preventing diseases such as autoimmunity and lymphoma. In T lymphocytes, the scaffold protein signaling hub CARD11 mediates NF-κB, JNK, mTOR pathway downstream of cell receptor (TCR) engagement. We recently identified QRICH1 a previously unrecognized interactor recruited to complex TCR engagement discovered that levels are upregulated in wild-type activated mouse primary CD8+ cells. Overexpression 293T Jurkat cells dose-dependently inhibited NF-κB by well constitutively active oncogenic mutants. QRICH1-deficient had increased IL-2 secretion stimulation. To study vivo role immunity, we generated novel conditional KO model. Compared control mice, mice decreased splenic CD4+ cells, despite no differences thymic CD4+, CD8+, or CD4+CD8+ populations. The population was skewed towards an effector memory phenotype. proliferation production pro-inflammatory cytokines IFN-γ TNF-α response ex stimulation with anti-CD3/CD28, OT-1 also cytokine antigen-specific Ova peptide. Our findings reveal negatively regulates modulating CARD11’s output. This work supported NIH grants R01AI148143, F31CA254167, T32GM007445.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.154.25