T-cell expression of Bruton's tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia.

T-cell expression of Bruton's tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia. Cell Mol Immunol. 2019 Aug 20;: Authors: Xia S, Liu X, Cao X, Xu S Abstract The role of Bruton's tyrosine kinase (BTK) in BCR signaling is well defined, and BTK is involved in B-cell development, differentiation, and malignancies. However, the expression of Btk in T cells and its role in T-cell function remain largely unknown. Here, we unexpectedly found high expression and activation of BTK in T cells. Deficiencies in BTK resulted in the impaired activation and proliferation of autoreactive T cells and ameliorated bone marrow failure (BMF) in aplastic anemia. Mechanistically, BTK is activated after TCR engagement and then phosphorylates PLCĪ³1, thus promoting T-cell activation. Treatment with acalabrutinib, a selective BTK inhibitor, decreased T-cell proliferation and ameliorated BMF in mice with aplastic anemia. Our results demonstrate an unexpected role of BTK in optimal T-cell activation and in the pathogenesis of autoimmune aplastic anemia, providing insights into the molecular regulation of T-cell activation and the pathogenesis of T-cell-mediated autoimmune disease. PMID: 31431692 [PubMed - as supplied by publisher]
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research