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- W4313348242 abstract "Abstract Introduction: Calcineurin (CN), a protein phosphatase activated by Ca2+-calmodulin, is involved in activation of NFAT. CN inhibitors such as cyclosporine A (CsA) and FK506 are potent inhibitors of T-cell responses and are commonly used to prevent graft rejection. Consistently, CNAβ-deficient mice exhibit defective thymocyte maturation in young mice. However, T cells undergo spontaneous activation in older Cnab-/- mice, and succumb to B-cell lymphomas. Methods: Splenocytes are cultured in the presence of anti-CD3/CD28 beads, TGFβ1 and IL-2 for 3 days. Cytokines in culture supernatants are determined by ELISA, CBA and MSD methods. Cells are stained with CD4, CD25, CD62L and intracellular FOXP3. Results: We observed that FOXP3+ Treg cells are decreased while mature activated T cells (CD62L-CD44+) are increased in KO mice compared to control mice. While TGFβ1 induced the expression of FOXP3 in WT cultures, it failed to induce FOXP3 in KO cultures. Cytokine profiles revealed that CNAβ is required to inhibit IL-4, IL-6, IL-10, IL-17 and IFNγ by TGFβ1. IHC analyses of lymphomas revealed that the lymphomas are of B cell origin and they do not express FOXP1, a marker for activated B cells (ABCs). Discussion: These data show that CNAβ is important for the development and homeostasis of mature T cells and Treg cells. The data also suggest that in the absence of CNAβ, a defective T-cell regulation results in activation of T cells, production of inflammatory cytokines and cause cancer." @default.
- W4313348242 created "2023-01-06" @default.
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- W4313348242 date "2010-04-01" @default.
- W4313348242 modified "2023-09-25" @default.
- W4313348242 title "Calcineurin Aβ signalling is required for Treg-cell generation and prevention of T-cell activation and B-cell lymphomagenesis (100.13)" @default.
- W4313348242 doi "https://doi.org/10.4049/jimmunol.184.supp.100.13" @default.
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