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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-leukocyte-associated-immunoglobulin-like-receptor-1-lair-1-in-collagen-induced-arthritis/