Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 8, Pages 2692-2700Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700271
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Funding
- U.S. Public Health Service [AR064825, AR069010, AR064723]
- Department of Veterans Affairs
- Arthritis Foundation
- National Institute of Allergy and Infectious Diseases intramural research program
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Several observations implicate a critical role for T cell dysregulation as a central problem in rheumatoid arthritis. We investigated a mechanism for suppressing T cell activation by stimulating a natural inhibitory receptor called leukocyte-associated Ig-like receptor-1 (LAIR-1). The collagen-induced arthritis (CIA) model and DR-1 transgenic mice were used to study the importance of LAIR-1 in autoimmune arthritis. Splenocytes from wild-type or LAIR-1(-/-) mice were stimulated with soluble anti-CD3 Ab in the presence or absence of alpha 1(II) and supernatants were collected for cytokine analysis. B6. DR1 mice were immunized with type II collagen/CFA to induce arthritis and were treated with either the stimulatory mAb to LAIR-1 or a hamster IgG control. Finally, B6. DR1/LAIR-1 (-/-) and B6. DR1/LAIR-1(+/+) mice were challenged for CIA and mean severity scores were recorded thrice weekly. Using splenocytes or purified CD4(+) cells that were sufficient in LAIR-1, CD3-induced cytokine secretion was significantly suppressed in the presence of collagen, whereas LAIR-1-deficient splenocytes had no attenuation. Treatment with a stimulatory mAb to LAIR-1 also significantly attenuated CIA in the LAIR(+/+) mice. When B6. DR1/LAIR-1(-/-) mice were immunized with type II collagen they developed more severe arthritis and had a greater percentage of affected limbs than the wild-type mice. These data demonstrate that collagen can suppress the T cell cytokine response through the action of LAIR-1. Treatment with stimulating LAIR-1 Abs suppresses CIAwhereas B6. DR1/LAIR-1(-/-) mice develop more severe arthritis than wild-type controls. These data suggest that LAIR-1 may be a potential therapeutic target for suppressing rheumatoid arthritis.
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