Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice.

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.

journal_name

Int Immunol

journal_title

International immunology

authors

Ishizaki M,Muromoto R,Akimoto T,Ohshiro Y,Takahashi M,Sekine Y,Maeda H,Shimoda K,Oritani K,Matsuda T

doi

10.1093/intimm/dxr057

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

575-82

issue

9

eissn

0953-8178

issn

1460-2377

pii

dxr057

journal_volume

23

pub_type

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