ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2553

Involvement of M2 Macrophages in the Pathogenesis of Arthritis in a Mouse Model

Shinjiro Kaieda1, Naomi Yoshida2, Yukiko Kunitake3, Daisuke Wakasugi4, Yukio Fujiwara5, Yoshihiro Komahara6, Hiroaki Ida7 and Tomoaki Hoshino2, 1Department of Medicine, *Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, kurume, Japan, 2Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan, 3Kurume University School of Medicine, Kurume, Japan, 4Medecine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan, 5Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan, 6Cell Pathology, Graduate School of Medical Sciences, Kurume University, Kumamoto, Japan, 7Respiorogy, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords:

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Animal Models Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Synovial lining macrophages play an important role in initiating and maintaining joint inflammation in arthritis. Classically activated pro-inflammatory macrophages and alternatively activated anti-inflammatory macrophages are generally referred to as M1 and M2 macrophages, respectively. The CD163, CD204, and CD206 proteins are predominantly expressed by M2-phenotype macrophages. Monocyte/macrophage-restricted expression of CD163 has been confirmed and observed in affected joint tissues of patients with RA and spondyloarthropathy. However, the pathogenic role of M2 macrophages in inflammatory arthritis remains unclear. We investigated the involvement of M2 macrophages in the development of arthritis in mice.

Methods:

 Collagen antibody-induced arthritis (CAIA) was induced using a combination of monoclonal anti-type II collagen antibodies and lipopolysaccharide. C57BL/6 (B6) background CD163 knockout (KO) mice and BALB/c background CD204 KO mice were used in an autoantibody-induced RA mouse model. Arthritis was graded using a 0–16 clinical scale (0–4 per paw). Histological assessment was conducted using paraffin-embedded 4-mm sections stained with hematoxylin and eosin.  Total RNA was isolated from mouse ankle joints. Gene expression of M2 macrophage markers including CD163, CD204, and CD206 and the pro-inflammatory cytokines IL-1β and IL-6 was determined before and 10 days after CAIA induction by quantitative RT-PCR.

Results:

CD163 gene expression in inflamed synovium was significantly lower than that in normal synovium. In contrast, CD204 mRNA expression was significantly greater in inflamed synovium. No significant differences in CD206 mRNA expression were observed between normal and inflamed synovium. Thus, we focused our attention on involvement of CD163- and CD204-positive macrophages in the development of arthritis. CD163 KO mice exhibited significantly higher clinical scores for arthritis than did control wild-type B6 mice. Histomorphometric quantification of arthritic changes in the joint tissues confirmed the clinical assessment, with higher inflammation in CD163 KO mice. Correspondingly, mRNA expression of IL-1β and IL-6 was significantly up-regulated in inflamed ankle joints of CD163 KO mice compared to those of control mice. CD204 KO mice were found to be normally susceptible to arthritis.

Conclusion:

 In the present study, we aimed to identify the involvement of M2 macrophages in CAIA. CD163 deficiency exacerbated disease severity in autoantibody-induced arthritis via up-regulation of synovial tissue IL-1β and IL-6 expression. Thus, CD163-positive M2 macrophages may play a role in inhibiting the pathogenesis of RA.

Disclosure: S. Kaieda, None; N. Yoshida, None; Y. Kunitake, None; D. Wakasugi, None; Y. Fujiwara, None; Y. Komahara, None; H. Ida, None; T. Hoshino, None.

To cite this abstract in AMA style:

Kaieda S, Yoshida N, Kunitake Y, Wakasugi D, Fujiwara Y, Komahara Y, Ida H, Hoshino T. Involvement of M2 Macrophages in the Pathogenesis of Arthritis in a Mouse Model [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/involvement-of-m2-macrophages-in-the-pathogenesis-of-arthritis-in-a-mouse-model/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/involvement-of-m2-macrophages-in-the-pathogenesis-of-arthritis-in-a-mouse-model/