Myeloid IPMK promotes the resolution of serum transfer-induced arthritis in mice

Animal Cells and Systems

Jong Seong Roh¹  Hyoungjoon Ahn²  Seulgi Lee²  Seyun Kim²  Jiyoon Beon²  Beomgu Lee³  Dong Hyun Sohn³ 

[1] Daegu Haany University;Korea Advanced Institute of Science and Technology (KAIST);Pusan National University School of Medicine;

关键词: rheumatoid arthritis;    inflammation;    inositol polyphosphate;    resolution;    ipmk;   

DOI  :  10.1080/19768354.2021.1952305

来源: DOAJ

【 摘 要 】

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by widespread joint inflammation, which leads to joint damage, disability, and mortality. Among the several types of immune cells, myeloid cells such as macrophages are critical for controlling the pathogenesis of RA. Inositol phosphates are water-soluble signaling molecules, which are synthesized by a series of enzymes including inositol phosphate kinases. Previous studies revealed actions of inositol phosphates and their metabolic enzymes in the modulation of inflammation such as Toll-like receptor-triggered innate immunity. However, the physiological roles of inositol polyphosphate (IP) metabolism in the regulation of RA remain largely uncharacterized. Therefore, our study sought to determine the role of inositol polyphosphate multikinase (IPMK), a key enzyme for IP metabolism and various cellular signaling control mechanisms, in mediating RA. Using myeloid cell-specific IPMK knockout (KO) mice, arthritis was induced via intraperitoneal K/BxN serum injection, after which disease severity was evaluated. Both wild-type and IPMK KO mice developed similar RA phenotypes; however, conditional deletion of IPMK in myeloid cells led to elevated arthritis scores during the resolution phase, suggesting that IPMK deficiency in myeloid cells impairs the resolution of inflammation. Bone marrow-derived IPMK KO macrophages exhibited no apparent defects in immunoglobulin Fc receptor (FcR) activation, osteoclast differentiation, or resolvin signaling. Taken together, our findings suggest that myeloid IPMK is a key determinant of RA resolution.

【 授权许可】

Unknown