Journal Article

TIARP attenuates autoantibody-mediated arthritis via the suppression of neutrophil migration by reducing CXCL2/CXCR2 and IL-6 expression

松本 功, Tanaka Yuki, 住田 孝之, Inoue Asuka, Sumida Takayuki, Ebe Hiroshi, Yoshida Hiroto, 瀬川 誠司, Matsumoto Isao, Matsumoto Yoshihiro, Kawaguchi Hoshimi, Takai Chinatsu, Umeda Naoto, Takahashi Satoru, Segawa Seiji, 高橋 智

2016

Overview

TNFα-induced adipose-related protein (TIARP) is a six-transmembrane protein expressed on macrophages, neutrophils and synoviocytes. We reported recently that mice deficient in TIARP (TIARP−/−) spontaneously develop arthritis and are highly susceptible to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effects of TIARP on neutrophils and fibroblast-like synoviocytes (FLS) have not been elucidated. We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP−/− mice. Arthritis in TIARP−/− mice transferred with K/BxN serum was significantly exacerbated compared with WT mice. We characterized the differences in neutrophils between wild-type (WT) and TIARP−/− mice by DNA microarray. Overexpression of CXCR1 and CXCR2 was noted in TIARP−/− neutrophils. Neutrophils of TIARP−/− mice showed strong migration activity, which was markedly facilitated by CXCL2 in vitro and in vivo. Moreover, enhanced production of CXCL2 and IL-6 and cell proliferation was noted in TIARP−/− TNFα-stimulated FLS. Blockade of IL-6R significantly attenuated serum-transferred TIARP−/− arthritis with diminished neutrophil recruitment in joints. Our findings suggested that TIARP independently down-regulated CXCL2 and IL-6 production by FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, with resultant reduction of neutrophil migration into arthritic joints.

• Publisher: Nature Publishing Group