IL-23 licenses the transition from preclinical autoimmunity to inflammatory arthritis through IL-17A-dependent mechanisms

Sustained IL-23 overexpression in C57BL/6 mice converts mild collagen-induced arthritis into highly penetrant inflammatory arthritis with increased innate mediators and IL-17A production.

• Why it matters: The transition from systemic autoimmunity to clinical rheumatoid arthritis is poorly understood, limiting early identification and targeted prevention of inflammatory arthritis.
• What they did: Collagen-induced arthritis was induced in less susceptible C57BL/6 mice with sustained systemic IL-23 overexpression, and IL-17A was tested using neutralizing anti-IL-17A antibody; human validation used whole-blood longitudinal transcriptomics in first-degree relatives (n=1080) and synovial RNA-seq (n=218).
• The result: IL-17A neutralization prevented arthritis development, and in humans lower RORC and KLRB1 expression associated with higher RA onset while synovium showed increased IL23R, IL23A, and CCR2, with higher IL23R in early versus established RA.

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