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Dysregulation of the PD-1/PD-L1 pathway contributes to the pathogenesis of celiac disease

Cellular & Molecular Immunology volume 16, pages 777–779 (2019)Cite this article

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In this study, we focus on the alteration of the programmed cell death 1 (PD-1)/PD-L1 pathway in celiac disease. We discuss the diverse roles of the PD-1 pathway in regulating immune responses and how this knowledge can improve celiac disease (CD) autoimmunity. The PD-1 and PD-L1 levels in the serum and in intestinal biopsies of CD patients may be relevant to the determination of a possible correlation between markers of the autoimmune response, inflammation, and disease activity. In previous work, we assessed the function of the IL-33/ST2 axis in the pathogenesis of CD.1 These data point to a possible important interregulation of IFN-γ and IL-33 in CD. IFN-γ can induce IL-33 expression and may contribute to IL-33 release via its proapoptotic effect in the intestinal mucosa.1 When IL-33 is released from cells, it can act on T cells to produce IFN-γ and can establish the ideal conditions for blocking the immune response through the PDL/PD-1 axis. Therefore, CD4+T cells lacking PD-1 have a significantly reduced likelihood of becoming regulatory cells.

CD is a chronic inflammatory disorder with autoimmune disease features that results from a loss of gluten tolerance.2,3 Intestinal damage is caused by CD4+T cells, which recognize deamidated gluten peptides presented in complex with HLA-DQ2.5, HLA-DQ2.2, and/or HLA-DQ8.4,5 Upon activation, these cells secrete high levels of IFN-γ, support B cell-mediated production of antibodies to tTG, modify gluten peptides, and enhance the lysis of stressed epithelial cells by CD8+T cells.5,6 The active state of CD has been associated with impairments in regulatory T-cell (Treg) function.7 Although the effector T-cell response in CD patients is well characterized, the role of Treg cells in the loss of tolerance to gluten remains poorly understood. These findings emphasize the hypothesis that innate defects in the Treg cell population eventually trigger inefficient immune regulation.

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Acknowledgements

The authors thank Ricardo Oya (Scientific Instrumentation Center, University of Jaén) for flow cytometry analysis. This work was supported by Research group BIO220, Junta de Andalucía.

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Authors and Affiliations

  1. Department of Experimental Biology, University of Jaén, Jaén, Spain

    Candelaria Ponce de León, Pedro Lorite, Teresa Palomeque & María Isabel Torres

  2. Department of Pediatrics Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain

    Miguel Angel López-Casado

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  1. Candelaria Ponce de León
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  2. Miguel Angel López-Casado
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  3. Pedro Lorite
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  5. María Isabel Torres
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Correspondence to María Isabel Torres.

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Ponce de León, C., Angel López-Casado, M., Lorite, P. et al. Dysregulation of the PD-1/PD-L1 pathway contributes to the pathogenesis of celiac disease. Cell Mol Immunol 16, 777–779 (2019). https://doi.org/10.1038/s41423-019-0256-7

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