[HTML][HTML] Targeting CD6 attenuates murine collagen induced arthritis

Y Li, JH Ruth, SM Rasmussen… - Arthritis & …, 2020 - ncbi.nlm.nih.gov
Y Li, JH Ruth, SM Rasmussen, KS Athukorala, DP Weber, MA Amin, PL Campbell
Arthritis & rheumatology (Hoboken, NJ), 2020ncbi.nlm.nih.gov
Background: CD6 is an important regulator of T cell function that interacts with the ligands
CD166 and CD318. To further clarify the significance of CD6 in rheumatoid arthritis (RA), we
examined the effects of targeting CD6 in the mouse collagen-induced arthritis (CIA) model,
using CD6 knockout (KO) mice and CD6 humanized mice that express human CD6 in lieu of
mouse CD6 on their T cells. Methods: We immunized wild type (Wt) and CD6 gene KO mice
with a collagen emulsion to induce CIA. For treatment studies using humanized CD6 mice …
Abstract
Background:
CD6 is an important regulator of T cell function that interacts with the ligands CD166 and CD318. To further clarify the significance of CD6 in rheumatoid arthritis (RA), we examined the effects of targeting CD6 in the mouse collagen-induced arthritis (CIA) model, using CD6 knockout (KO) mice and CD6 humanized mice that express human CD6 in lieu of mouse CD6 on their T cells.
Methods:
We immunized wild type (Wt) and CD6 gene KO mice with a collagen emulsion to induce CIA. For treatment studies using humanized CD6 mice, mice were immunized similarly and UMCD6 (a mouse anti-human CD6 IgG) 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 CIA Wt and CD6 KO mice.
Results:
Absence of CD6 reduced 1) collagen-specific Th9 and Th17, but not Th1 responses, 2) many pro-inflammatory joint cytokines, 3) serum levels of collagen-reactive total IgG and IgG1, but not IgG2a and IgG3. Joint homogenate hemoglobin (Hb) content was significantly reduced in CIA CD6 KO compared to Wt mice (reduced angiogenesis). Moreover, treating CD6 humanized mice with mouse anti-human CD6 monoclonal antibody (mAb) was similarly effective in reducing joint inflammation in CIA.
Conclusions:
Taken together, these data suggest that interaction of CD6 with its ligands is important for perpetuation of CIA and other inflammatory arthritides that are T cell driven.
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