Malt1 inactivation attenuates experimental colitis through the regulation of Th17 and Th1/17 cells

Protease activity of MALT lymphoma-translocation protein 1 (Malt1) plays an important role in the development of colitis, but the detailed mechanism has not been fully elucidated.

Effects of Malt1 protease on the activation of T cells and the development of experimental colitis was investigated using Malt1 protease-deficient (PD) mouse.

IL-2 production from CD4⁺ T cells of Malt1 PD mice was decreased compared with that of wild-type (WT) mice. Intraperitoneal injection of anti-CD3 antibody into Malt1 PD mouse induced less productions of IL-17 in the plasma, as well as the colonic gene expression of IL-17A, compared with WT mice, whereas IFN-γ production was not impaired. In naïve T-cell transfer colitis model, Malt1 PD T cells induced less disease severity than WT T cells. Then, reduction in the populations of Th17 and Th1/17 cells was observed in the mesenteric lymph nodes of the recipient mice transferred with Malt1 PD T cells, whereas those of Th1 cells were not impaired. IL-17A expression in the colon was also decreased in the mouse receiving Malt1 PD T cells.

Inactivation of Malt1 protease activity abrogates Th17 and Th1/17 cell activation, resulting in the amelioration of experimental colitis.