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Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice
Yawei Liu, … , Rikard Holmdahl, Shohreh Issazadeh-Navikas
Yawei Liu, … , Rikard Holmdahl, Shohreh Issazadeh-Navikas
Published December 13, 2010
Citation Information: J Clin Invest. 2011;121(1):249-264. https://doi.org/10.1172/JCI43964.
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Research Article Immunology

Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

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Abstract

NKT cells in the mouse recognize antigen in the context of the MHC class I–like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707–721), was not associated with either MHC class I or II. Activation of CD1d-restricted mCII707–721–specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707–721–specific NKT cells induced T cell death through Fas/FasL, in an IL-17A–independent fashion. Moreover, mCII707–721–specific NKT cells suppressed a range of in vivo inflammatory conditions, including delayed-type hypersensitivity, antigen-induced airway inflammation, collagen-induced arthritis, and EAE, which were all ameliorated by mCII707-721 vaccination. The findings presented here offer new insight into the intrinsic roles of NKT cells in health and disease. Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases.

Authors

Yawei Liu, Anna Teige, Emma Mondoc, Saleh Ibrahim, Rikard Holmdahl, Shohreh Issazadeh-Navikas

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Figure 12

Activation of mCII707–721–specific NKT cells suppresses arthritis.

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Activation of mCII707–721–specific NKT cells suppresses arthritis.
   
(...
(A) Prevaccination of B10.Q mice with mCII707–721 significantly reduced severity by CIA clinical scoring compared with control peptide (mCI707–721) vaccination (14 mice per mCI707–721 group, 19 mice per mCII707–721 group; *P ≤ 0.05). (B) Histological arthritic scores by H&E staining of joints. Data are mean ± SD, n = 5. **P ≤ 0.01. (C) Histological scores of percentage of IFN-γ–, IL-4–, and TNF-α–positive cells were significantly reduced in the mCII707–721–vaccinated group. Data are mean ± SD, n = 5. *P ≤ 0.05. (D) Suppression of arthritis was associated with reduced CD4+ T cell–infiltrating cells, IFN-γ–, and IL-4–producing cells by immunohistochemistry staining of joints. Red-brown color shows positively stained cells. Scale bar: 100 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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