IL-33 exacerbates autoantibody-induced arthritis

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• Rheumatoid arthritis involves complex immune dysregulation.
• Identifying factors integrating innate and adaptive immunity is crucial for understanding RA.

Purpose of the Study:

• To investigate the role of Interleukin-33 (IL-33) in anti-glucose-6-phosphate isomerase autoantibody-induced arthritis (AIA).
• To elucidate the mechanism by which IL-33 influences inflammatory arthritis.

Main Methods:

• Utilized ST2-deficient (ST2(-/-)) and mast cell-deficient mice models.
• Administered recombinant IL-33 (rIL-33) to wild-type and knockout mice.
• Assessed arthritis severity, cytokine expression, and mast cell degranulation in vitro and in vivo.

Main Results:

• ST2(-/-) mice exhibited attenuated AIA and reduced proinflammatory cytokines.
• rIL-33 treatment exacerbated AIA and enhanced cytokine production in wild-type mice.
• IL-33-mediated exacerbation was dependent on ST2 and mast cells, which showed enhanced degranulation.

Conclusions:

• IL-33 exacerbates autoantibody-mediated arthritis by promoting mast cell degranulation and cytokine production.
• Synovial fibroblast-derived IL-33 represents a novel mechanism regulating adaptive immune responses via innate cell activation in inflammatory arthritis.