The Role of Leukocyte-Associated Ig-like Receptor-1 in Suppressing Collagen-Induced Arthritis
| Autor: | Savannah L. Smith, Linda K. Myers, Seunghyun Kim, Edward F. Rosloniec, Lauren C. Price, David D. Brand, John M. Stuart, John E. Coligan, Andrew H. Kang, Jeoung-Eun Park, Ellis R. Easterling |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases CD4-Positive T-Lymphocytes medicine.medical_specialty medicine.medical_treatment T cell Immunology Type II collagen Arthritis Mice Transgenic Article Immune tolerance Arthritis Rheumatoid 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Immune Tolerance Immunology and Allergy Animals Humans Receptors Immunologic Receptor Collagen Type II Cells Cultured Mice Knockout business.industry medicine.disease Arthritis Experimental Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Cytokine medicine.anatomical_structure Rheumatoid arthritis Cytokine secretion business 030215 immunology HLA-DRB1 Chains |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 199(8) |
| ISSN: | 1550-6606 |
| Popis: | 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 α1(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 CIA whereas 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. |
| Databáze: | OpenAIRE |
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