AUTHOR=Moon Young-Mee , Lee Seon-Yeong , Kwok Seung-Ki , Lee Seung Hoon , Kim Deokhoon , Kim Woo Kyung , Her Yang-Mi , Son Hea-Jin , Kim Eun-Kyung , Ryu Jun-Geol , Seo Hyeon-Beom , Kwon Jeong-Eun , Hwang Sue-Yun , Youn Jeehee , Seong Rho H. , Jue Dae-Myung , Park Sung-Hwan , Kim Ho-Youn , Ahn Sung-Min , Cho Mi-La 

TITLE=The Fos-Related Antigen 1–JUNB/Activator Protein 1 Transcription Complex, a Downstream Target of Signal Transducer and Activator of Transcription 3, Induces T Helper 17 Differentiation and Promotes Experimental Autoimmune Arthritis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01793

DOI=10.3389/fimmu.2017.01793

ISSN=1664-3224

ABSTRACT=<p>Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders. Signal transducer and activator of transcription 3 (STAT3) orchestrates the expression of proinflammatory cytokines and pathogenic cell differentiation from interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3 signaling are not fully understood. Here, we observed that Fos-related antigen 1 (FRA1) and JUNB are directly involved in STAT3 binding to sites in the promoters of <italic>Fosl1</italic> and <italic>Junb</italic>. Promoter binding increased expression of IL-17 and the development of Th17 cells. Overexpression of <italic>Fra1</italic> and <italic>Junb</italic> in mice resulted in susceptibility to collagen-induced arthritis and an increase in Th17 cell numbers and inflammatory cytokine production. In patients with rheumatoid arthritis, FRA1 and JUNB were colocalized with STAT3 in the inflamed synovium. These observations suggest that FRA1 and JUNB are associated closely with STAT3 activation, and that this activation leads to Th17 cell differentiation in autoimmune diseases and inflammation.</p>