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Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells

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Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease mediated by T cells. Collagen type II (CII) is one of the autoantigens associated with RA. CII263-272 is a predominant CII antigenic peptide that can induce T-cell activation upon binding to MHC and interaction with the appropriate T-cell receptor (TCR). Altered CII263-272 peptides with substitution of specific amino acids could bind to RA-associated HLA-DR4/1 with no T cell stimulating effects and could inhibit T cell activation in RA. We performed this study to evaluate the effect of mucosal administration and to explore the mechanism of the inhibitory effect of altered CII263-272 peptide (267Q → A, 270K → A and 271G → A) on collagen induced arthritis (CIA). CIA was induced in Lewis rats by immunization with bovine CII. Altered CII263-272 peptide was given intranasally beginning from arthritis onset. Wild CII263-272 peptide or PBS was administered as controls. Therapeutic effects were evaluated by arthritis scores, body weight change, and joint pathologic scores. The anti-CII antibody and its subtypes and the cytokines, IFN-γ, IL-10, and IL-17 were measured with ELISA. Foxp3+CD4+CD25+ regulatory T cell induction was assessed by FACS analysis. Following treatment with the altered CII263-272 peptide, arthiritis scores were reduced and body weight was increased. The altered CII263-272 peptide could retard the histologic lesion of the joints. The titers of anti-CII antibodies IgG2a in altered CII263-272 peptide treated rats decreased markedly compared to PBS-treated rats. The serum levels of IFN-γ in rats treated with altered peptide was lower than that of rats treated with wild CII263-272 peptide and PBS. No differences were observed in the levels of serum IL-10 among the three groups. The altered CII263-272 peptide could decrease serum level of IL-17 and increase peripheral Foxp3+CD4+CD25+ T cells at early stage of CIA. Mucosal administration of altered CII263-272 peptide could effectively inhibit the progression of CIA. Altered CII263-272 peptide could suppress Th17 cells and expand regulatory T cells in the early stage of the disease. The IgG2a subtype of anti-CII antibodies and IFN-γ were reduced and in vivo Th1 responses were inhibited as a result of altered CII peptide treatment. Altered CII peptide is likely therapeutic in RA.

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Acknowledgments

This work was partially supported by grants from the National Natural Science Foundation of China (No.30671933 and No.30430290).

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, People’s Hospital, Peking University Medical School, 11 Xizhimen South St., Beijing, 100044, China

    Jinxia Zhao, Ru Li, Jing He, Jinxia Shi, Li Long & Zhanguo Li

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  1. Jinxia Zhao
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Correspondence to Zhanguo Li.

Additional information

ZJX, carried out the experiments and drafted the manuscript. HJ, SJX and LL performed the experiments in coordination. LR and LZG provided experimental design and supervision. All authors read and approved the final manuscript.

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Zhao, J., Li, R., He, J. et al. Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells. Rheumatol Int 29, 9–16 (2008). https://doi.org/10.1007/s00296-008-0634-4

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