MICL controls inflammation in rheumatoid arthritis

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C-type lectin receptor (CLR) predominantly expressed on myeloid cells.
• Previous research suggests MICL plays a role in controlling inflammation.

Purpose of the Study:

• To investigate the role of MICL in inflammatory pathology using Clec12A knockout mice.
• To explore MICL's involvement in rheumatoid arthritis (RA) pathogenesis.

Main Methods:

• Utilized Clec12A(-/-) mice in a collagen antibody-induced arthritis (CAIA) model.
• Employed clinical scoring, histology, flow cytometry, bone-marrow chimeras, blocking antibodies, and in vivo imaging.
• Analyzed MICL in RA patients via immunohistochemistry, SNP analysis, and detected anti-MICL autoantibodies using ELISA and dot-blot.

Main Results:

• MICL-deficient mice showed exacerbated inflammation in CAIA due to inappropriate myeloid cell activation.
• No association found between MICL polymorphisms and RA disease.
• MICL was identified as a target of autoantibodies in a subset of RA patients, recapitulating the knockout phenotype in wild-type mice when these antibodies were administered.

Conclusions:

• MICL is crucial for regulating inflammation in arthritis and acts as an autoantigen in some RA patients.
• This study reveals a novel mechanism in RA pathogenesis involving autoantibodies against inhibitory receptors on myeloid cells.