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Updated: May 31, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice
Masayuki Ishizaki1, Ryuta Muromoto, Toshihiko Akimoto
1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Abstract:
Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive swelling and erythema by arthritogenic antibody injection, whereas Tyk2-deficient mice did not show any signs of arthritis. Indeed, neither the infiltration of inflammatory cells nor the fibrillation of articular cartilages was observed in Tyk2-deficient mice. Tyk2 deficiency also reduced the production of T(h)1/T(h)17-related cytokines, the other proinflammatory cytokines and matrix metalloproteases, which are induced in the CAIA paw. Our results demonstrate a critical contribution of Tyk2 in the development of arthritis, and we propose that Tyk2 might be an important candidate for drug development.
Insights
Tyrosine kinase-2 (Tyk2) is crucial for arthritis development. Tyk2-deficient mice showed no arthritis symptoms, indicating Tyk2
Area of Science:
- Immunology
- Rheumatology
Background:
- Tyrosine kinase-2 (Tyk2) is involved in cytokine signaling in immune responses.
- Cytokine signaling plays a role in the pathogenesis of autoimmune diseases like arthritis.
Purpose of the Study:
- To investigate the role of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) in vivo.
- To determine if Tyk2 deficiency protects against arthritis development.
Main Methods:
- Utilized Tyk2-deficient mice and wild-type littermates.
- Induced arthritis using anti-type II collagen antibodies (CAIA model).
- Assessed clinical signs of arthritis, inflammatory cell infiltration, cartilage fibrillation, and cytokine/matrix metalloprotease production.
Main Results:
- Wild-type mice developed severe arthritis with swelling and erythema.
- Tyk2-deficient mice exhibited no signs of arthritis, inflammation, or cartilage damage.
- Tyk2 deficiency significantly reduced pro-inflammatory cytokines (Th1/Th17) and matrix metalloproteases in the affected paws.
Conclusions:
- Tyk2 plays a critical role in the development of CAIA.
- Tyk2 deficiency confers protection against arthritis.
- Tyk2 is a potential therapeutic target for drug development in arthritis treatment.
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