Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice

Arthritis Rheum. 2009 Feb;60(2):390-5. doi: 10.1002/art.24220.


Objective: To investigate the role of interleukin-22 (IL-22) in collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis.

Methods: C57BL/6 mice were immunized with type II collagen (CII) in Freund's incomplete adjuvant with added Mycobacterium tuberculosis, and levels of IL-22 and its specific receptor, IL-22 receptor type I (IL-22RI), were measured in sera and tissue by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction analysis. Clinical and histologic signs of arthritis were recorded and compared with those in C57BL/6 mice deficient in the IL-22 gene (IL-22(-/-)). Humoral and cellular immune responses against CII were analyzed. In vitro osteoclastogenesis assays were performed on splenocytes.

Results: Upon immunization with CII in Freund's incomplete adjuvant plus heat-killed Mycobacterium tuberculosis, sera from C57BL/6 mice were found to contain high levels of IL-22, and the specific IL-22RI was expressed in lymphoid tissue, including splenocytes. IL-22(-/-) mice were less susceptible to CIA than were wild-type mice, as evidenced by their decreased incidence of arthritis and decreased pannus formation. Remarkably, the less severe form of arthritis in IL-22(-/-) mice was associated with increased production of CII-specific and total IgG antibodies, whereas cellular CII responses were unchanged. In vitro, IL-22 was found to promote osteoclastogenesis, a process that might contribute to its proinflammatory activity in CIA.

Conclusion: Endogenous IL-22 plays a proinflammatory role in CIA in C57BL/6 mice. Our data also indicate that IL-22 promotes osteoclastogenesis and regulates antibody production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / physiopathology
  • Cell Line
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / biosynthesis
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Isoenzymes / metabolism
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoclasts / drug effects
  • Osteoclasts / enzymology
  • Osteoclasts / immunology
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Recombinant Proteins / pharmacology
  • Spleen / drug effects
  • Spleen / enzymology
  • Spleen / immunology
  • Tartrate-Resistant Acid Phosphatase


  • Immunoglobulin G
  • Interleukins
  • Isoenzymes
  • RNA, Messenger
  • Receptors, Interleukin
  • Recombinant Proteins
  • interleukin-22 receptor
  • Macrophage Colony-Stimulating Factor
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • interleukin-22