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Role of Malt1 protease activity in pathogenesis of inflammatory disorders mediated by FcγR signaling.

Abstract：

:MALT lymphoma-translocation protein 1 (Malt1) protease activity is triggered by stimulation of various immune receptors. Activation of Malt1 protease induces cleavage of negative regulators for immune responses, resulting in lymphocytes activation. Although Malt1 protease mediates the signaling process downstream of the T cell, B cell, and dectin receptors, its contribution in Fcγ receptor (FcγR) signaling has not been elucidated. In this study, we investigated the role of Malt1 protease activity in FcγR signaling using Malt1 protease-deficient (PD) mouse. In addition, role of Malt1 protease for the development of FcγR-mediated autoimmune disease was also investigated in vivo. Malt1 protease cleaves their substrates, such as RelB and cylindromatosis (CYLD). However, the Malt1 proteolytic activity was silenced in the Malt1 PD mice. Production of inflammatory cytokines via FcγR stimulation was decreased on dendritic cells prepared from Malt1 PD mice. In FcγR-dependent murine immune thrombocytopenia (ITP) model, gene expressions of the inflammatory cytokines in the spleen of Malt1 PD mice were lower than those of WT mice. Then, Malt1 PD mice protected the development of thrombocytopenia. These results clearly figured out that Malt1 protease activity plays an important role in the activation of innate immune cells via FcγR, and the development of FcγR-mediated autoimmune diseases. Therefore, Malt1 is an attractive target for the treatment of inflammatory diseases mediated by FcγR.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Nakamura Y,Yokoyama K,Igaki K,Tsuchimori N

doi

10.1016/j.intimp.2018.01.028

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

193-196

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)30028-6

journal_volume

56

pub_type

杂志文章

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