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Attenuation of Murine Collagen‐Induced Arthritis by Targeting CD 6
Author(s) -
Li Yan,
Ruth Jeffrey H.,
Rasmussen Stephanie M.,
Athukorala Kalana S.,
Weber Daniel P.,
Amin M. Asif,
Campbell Phillip L.,
Singer Nora G.,
Fox David A.,
Lin Feng
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41288
Subject(s) - arthritis , proinflammatory cytokine , chemistry , microbiology and biotechnology , immunology , humanized mouse , knockout mouse , cytokine , rheumatoid arthritis , antibody , inflammation , immune system , biology , receptor , biochemistry
Objective CD 6 is an important regulator of T cell function that interacts with the ligands CD 166 and CD 318. To further clarify the significance of CD 6 in rheumatoid arthritis ( RA ), we examined the effects of targeting CD 6 in the mouse model of collagen‐induced arthritis ( CIA ), using CD 6‐knockout ( CD 6‐ KO ) mice and CD 6‐humanized mice that express human CD 6 in lieu of mouse CD 6 on their T cells. Methods We immunized wild‐type ( WT ) and CD 6 gene– KO mice with a collagen emulsion to induce CIA . For treatment studies using CD 6‐humanized mice, mice were immunized similarly and a mouse anti‐human CD 6 IgG ( UMCD 6) or control IgG was injected on days 7, 14, and 21. Joint tissues were evaluated for tissue damage, leukocyte infiltration, and local inflammatory cytokine production. Collagen‐specific Th1, Th9, and Th17 responses and serum levels of collagen‐specific IgG subclasses were also evaluated in WT and CD 6‐ KO mice with CIA . Results The absence of CD 6 reduced 1) collagen‐specific Th9 and Th17, but not Th1 responses, 2) the levels of many proinflammatory joint cytokines, and 3) serum levels of collagen‐reactive total IgG and IgG1, but not IgG2a and IgG3. Joint homogenate hemoglobin content was significantly reduced in CD 6‐ KO mice with CIA compared to WT mice with CIA ( P < 0.05) (reduced angiogenesis). Moreover, treating CD 6‐humanized mice with mouse anti‐human CD 6 monoclonal antibody was similarly effective in reducing joint inflammation in CIA . Conclusion Taken together, these data suggest that interaction of CD 6 with its ligands is important for the perpetuation of CIA and other inflammatory arthritides that are T cell driven.