Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Several observations implicate a critical role for T cell dysregulation as a central problem in RA. We present a method for suppressing T cell activation by activating natural inhibitory receptors called leukocyte associated immunoglobulin-like receptor-1 (LAIR-1). We used the collagen-induced arthritis model and DR-1 tg mice to study the importance of LAIR-1 in autoimmune arthritis.
Methods: a.) Murine splenocytes (LAIR-1 +/+ or LAIR-1 -/-) were stimulated with soluble CD3 in the presence or absence of collagen and supernatants were collected for cytokine analysis. b.) DR-1 mice were immunized with CII/CFA to induce arthritis and were injected intra-articularly with 0.3mg of either the stimulatory monoclonal antibody to LAIR-1 or a hamster IgG control. c.) DR1/LAIR-1 -/- and DR1/LAIR-1 +/+ mice were immunized to induce arthritis and mean severity scores were recorded thrice weekly.
Results: a.) In the presence of LAIR-1, CD3-induced cytokine secretion was significantly suppressed in the presence of collagen, while LAIR-1 -/- cells had no attenuation. b.) Treatment with the stimulatory monoclonal antibody to LAIR-1 attenuated CIA in the mice (severity scores 1.5 ± 1.9 vs. 6.4 ± 2.4, p = 0.007). c.) DR1/LAIR-1-/- mice that were immunized with CII developed more severe arthritis and had a greater percentage of limbs affected with arthritis than did the wild type (DR1/LAIR-1 +/+) group (p<0.05).
Conclusion: Taken together, these data demonstrate that collagen can suppress T cell cytokine response in the presence of LAIR-1. Treatment with stimulating mLAIR-1 antibodies suppresses CIA while 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 RA.
To cite this abstract in AMA style:Kim S, Coligan JE, Park JE, Stuart JM, Kang A, Myers L. The Role of Leukocyte Associated Immunoglobulin-like Receptor-1 (LAIR-1) in Collagen-Induced Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-role-of-leukocyte-associated-immunoglobulin-like-receptor-1-lair-1-in-collagen-induced-arthritis/. Accessed June 4, 2020.
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