Il27ra, encoding the IL-27 receptor alpha subunit, is crucial for IL-27 signaling. IL-27-IL-27Rα signaling is involved in multiple biological processes. It activates p38 MAPK-PGC-1α signaling in adipocytes, stimulating thermogenesis and energy expenditure, which is significant for maintaining body temperature and combating metabolic disorders like obesity [1]. It is also associated with the TNF-α→ERK→ETS1 pathway in hematopoietic stem cell (HSC) aging, where its deletion rescues HSC functional decline [2].

In Il27ra -deleted pregnant mice, the transfer of Ptgs2+/COX-2+ macrophages prevented fetal loss, indicating its role in decidualization and maternal-fetal tolerance [3]. In MM cell lines and primary MM cells, IL-27 can upregulate CD38 cell-surface expression via IL-27Rα, which may enhance CD38-directed monoclonal antibody therapies [4]. In IL27RA-deficient patients, the phosphorylation of STAT1 and STAT3 by IL-27 is abolished in T cells, leading to impaired expansion of anti-EBV effector cytotoxic CD8+ T cells [5]. Il27ra -/- γδ T cells are more pathogenic in a psoriasis model, while rmIL-27 injection ameliorates psoriatic inflammation [6]. C57BL/6 mice lacking Il27ra developed POI symptoms when on a high-fat diet, showing its role in ovarian function [7].

In conclusion, Il27ra is essential for IL-27 signaling and is involved in various biological processes such as adipocyte thermogenesis, HSC function, pregnancy maintenance, immune responses against EBV, and the regulation of skin inflammation and ovarian function. Gene knockout mouse models of Il27ra have significantly contributed to understanding its roles in metabolic disorders, hematopoietic diseases, pregnancy-related issues, infectious diseases, psoriasis, and premature ovarian insufficiency.