RANK⁺TLR2⁺ myeloid subpopulation converts autoimmune to joint destruction in rheumatoid arthritis.

ABSTRACT: Joint destruction is the major clinic burden in patients with rheumatoid arthritis (RA). It is unclear, though, how this autoimmune disease progresses to the point of deterioration of the joint. Here, we report that in a mouse model of RA the upregulation of TLR2 expression and its α(2,3) sialylation in RANK⁺ myeloid monocytes mediate the transition from autoimmunity to osteoclast fusion and bone resorption, resulting in joint destruction. The expression of α(2,3) sialyltransferases was significantly increased in RANK⁺TLR2⁺ myeloid monocytes, and their inhibition or treatment with a TLR2 inhibitor blocked osteoclast fusion. Notably, analysis of our single-cell RNA-sequencing (scRNA-seq) libraries generated from RA mice revealed a novel RANK⁺TLR2<

SUBMITTER: Zhang W 

PROVIDER: S-EPMC10299822 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature