AUTHOR=Han Liang , Chen Zhe , Yu Kun , Yan Jiahui , Li Tingting , Ba Xin , Lin Weiji , Huang Yao , Shen Pan , Huang Ying , Qin Kai , Geng Yinhong , Liu Yafei , Wang Yu , Tu Shenghao 

TITLE=Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.787252

DOI=10.3389/fimmu.2021.787252

ISSN=1664-3224

ABSTRACT=<p>The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway <italic>via</italic> the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients <italic>via</italic> different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4<sup>+</sup> T helper type 2 (Th2) cell, CD4<sup>+</sup> T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.</p>