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

• Published in: Scientific reports 2016-12, Vol.6 (1), p.38684-38684, Article 38684
• Main Authors: Inoue, Asuka, Matsumoto, Isao, Tanaka, Yuki, Umeda, Naoto, Takai, Chinatsu, Kawaguchi, Hoshimi, Ebe, Hiroshi, Yoshida, Hiroto, Matsumoto, Yoshihiro, Segawa, Seiji, Takahashi, Satoru, Sumida, Takayuki
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/21; 38; 38/61; 59; 631/250/38; 64/60; 692/4023/1670/498; Arthritis; Cell proliferation; Chemokine receptors; Collagen; CXCR2 protein; DNA microarrays; Humanities and Social Sciences; Interleukin 6; Joint diseases; Leukocyte migration; Leukocytes (neutrophilic); Macrophages; multidisciplinary; Neutrophils; Rodents; Science; Synoviocytes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38684

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.