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

Inoue, Asuka  ,  Matsumoto, Isao  ,  Tanaka, Yuki  ,  Umeda, Naoto  ,  Takai, Chinatsu  ,  Kawaguchi, Hoshimi  ,  Ebe, Hiroshi  ,  Yoshida, Hiroto  ,  Matsumoto, Yoshihiro  ,  Segawa, Seiji  ,  Takahashi, Satoru  ,  Sumida, Takayuki

6p.38684 , 2016-12 , Nature Publishing Group
ISSN:2045-2322
Description
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.
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