Bcl2L12 mediates effects of protease-activated receptor-2 on the pathogenesis of Th2-dominated responses of patients with ulcerative colitis.

The immune dysregulation plays an important role in the pathogenesis of ulcerative colitis (UC). Bcl2 like protein-12 (Bcl2L12) and mast cells are involved in immune dysregulation of UC. This study aims to elucidate the role of Bcl2L12 in the contribution to the pathogenesis of T helper (Th)2-biased inflammation in UC patients. The results showed that Bcl2L12 was expressed by peripheral CD4⁺ T cells that was associated with Th2 polarization in UC patients. Bcl2L12 mediated the protease-activated receptor-2 (PAR2)-induced IL-4 expression in CD4⁺ cells. Activation of PAR2 increased expression of Bcl2L12 in CD4⁺ T cells. Bcl2L12 mRNA decayed spontaneously in CD4⁺ T cells after separated from UC patients which was prevented by activating PAR2. Bcl2L12 mediated the binding between GATA3 and the Il4 promoter in CD4⁺ T cells. Mice with Bcl2L12 deficiency failed to induce Th2-biased inflammation in the colon mucosa. We conclude that CD4⁺ T cells from UC patients expressed high levels of Bcl2L12; the latter plays an important role in the development of Th2-biased inflammation in the intestine. Bcl2L12 may be a novel therapeutic target in the treatment of Th2-biased inflammation.

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