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


CONCLUSIONS
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.
Geboes
Lies
L
Katholieke Universiteit Leuven, Leuven, Belgium. lies.geboes@rega.kuleuven.be
Dumoutier
Laure
L
Kelchtermans
Hilde
H
Schurgers
Evelien
E
Mitera
Tania
T
Renauld
Jean-Christophe
JC
Matthys
Patrick
P
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D000071681:Tartrate-Resistant Acid Phosphatase; D000097043:Interleukin-22
D000135:Acid Phosphatase; D007074:Immunoglobulin G; D007378:Interleukins; D007527:Isoenzymes; D016173:Macrophage Colony-Stimulating Factor; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D000071681:Tartrate-Resistant Acid Phosphatase; D000097043:Interleukin-22; C415369:interleukin-22 receptor