TLR7 endogenous ligands remodel glycolytic macrophages and trigger skin-to-joint crosstalk in psoriatic arthritis.

ABSTRACT: Thirty percent of psoriasis patients develop psoriatic arthritis (PsA), nevertheless the mechanism remains unknown. Endogenous GU-rich miRNAs activate endosomal TLR7 that plays a critical role in autoimmune diseases. We found that endogenous TLR7 ligands, miR-29 and miR-Let7b, were markedly increased in PsA compared to osteoarthritis (OA) synovial fluid (SF)s. We showed that intradermal (i.d.) miR-Let7b injection promoted skin inflammation, which was characterized by amplified Th1 cells, CD68⁺ M1 macrophages, and transcriptional upregulation of glycolytic mediators, GLUT1, C-MYC, and HIF1α. Expansion of skin Th1 cells driven by miR-Let7b was also linked to elevated M1-associated IRFs. Interestingly, i.d. miR-Let7b administration exacerbated suboptimal joint inflammation along wi

SUBMITTER: Van Raemdonck K 

PROVIDER: S-EPMC10018531 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature