The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis

Seunghyun Kim, Ellis R. Easterling, Lauren C. Price, Savannah L. Smith, John E. Coligan, Jeoung Eun Park, David Brand, Edward F. Rosloniec, John M. Stuart, Andrew Kang, Linda Myers

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Abstract

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-12/2 mice were stimulated with soluble anti-CD3 Ab in the presence or absence of a1(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-12/2 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-12/2 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-12/2 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.

Original languageEnglish (US)
Pages (from-to)2692-2700
Number of pages9
JournalJournal of Immunology
Volume199
Issue number8
DOIs
StatePublished - Oct 15 2017

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Experimental Arthritis
Leukocytes
Arthritis
Collagen Type II
Cytokines
T-Lymphocytes
Rheumatoid Arthritis
Collagen
Cricetinae
Transgenic Mice
Extremities
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kim, S., Easterling, E. R., Price, L. C., Smith, S. L., Coligan, J. E., Park, J. E., ... Myers, L. (2017). The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis. Journal of Immunology, 199(8), 2692-2700. https://doi.org/10.4049/jimmunol.1700271

The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis. / Kim, Seunghyun; Easterling, Ellis R.; Price, Lauren C.; Smith, Savannah L.; Coligan, John E.; Park, Jeoung Eun; Brand, David; Rosloniec, Edward F.; Stuart, John M.; Kang, Andrew; Myers, Linda.

In: Journal of Immunology, Vol. 199, No. 8, 15.10.2017, p. 2692-2700.

Research output: Contribution to journalArticle

Kim, S, Easterling, ER, Price, LC, Smith, SL, Coligan, JE, Park, JE, Brand, D, Rosloniec, EF, Stuart, JM, Kang, A & Myers, L 2017, 'The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis', Journal of Immunology, vol. 199, no. 8, pp. 2692-2700. https://doi.org/10.4049/jimmunol.1700271
Kim S, Easterling ER, Price LC, Smith SL, Coligan JE, Park JE et al. The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis. Journal of Immunology. 2017 Oct 15;199(8):2692-2700. https://doi.org/10.4049/jimmunol.1700271
Kim, Seunghyun ; Easterling, Ellis R. ; Price, Lauren C. ; Smith, Savannah L. ; Coligan, John E. ; Park, Jeoung Eun ; Brand, David ; Rosloniec, Edward F. ; Stuart, John M. ; Kang, Andrew ; Myers, Linda. / The role of leukocyte-associated Ig-like receptor-1 in suppressing collagen-induced arthritis. In: Journal of Immunology. 2017 ; Vol. 199, No. 8. pp. 2692-2700.
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abstract = "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-12/2 mice were stimulated with soluble anti-CD3 Ab in the presence or absence of a1(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-12/2 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-12/2 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-12/2 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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