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

Int Immunol. 2011 Sep;23(9):575-82. doi: 10.1093/intimm/dxr057. Epub 2011 Jul 16.


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.

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / genetics*
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / physiopathology
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Collagen Type II / immunology*
  • Cytokines / metabolism
  • Erythema
  • Gene Expression Regulation / immunology
  • Inflammation
  • Joints / immunology
  • Joints / metabolism*
  • Joints / pathology
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Knockout
  • TYK2 Kinase / genetics
  • TYK2 Kinase / immunology
  • TYK2 Kinase / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology


  • Antibodies
  • Collagen Type II
  • Cytokines
  • TYK2 Kinase
  • Tyk2 protein, mouse