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Immunopathogenesis of Celiac Disease

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Advances in Celiac Disease

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Abstract

Celiac disease (CD) is a systemic disorder with an immunological basis caused by an abnormal immune response to cereal gluten proteins, affecting to genetically susceptible individuals. The interaction of genetic and environmental factors leads to the loss of tolerance to these proteins and the development of an intestinal lesion characterized by lymphocyte infiltration, mucosal remodelling and epithelial destruction. The disease is now considered a model of autoimmunity driven by an environmental antigen from the diet. Gluten proteins are partially hydrolysed in the intestine forming large peptides which cross the epithelium and are translocated to the lamina propria, where an adaptive immune response is activated following the recognition by gluten-reactive CD4 + T cells of deamidated gluten T-cell epitopes bound to HLA-DQ molecules in the membrane of antigen presenting cells. Lamina propria CD4 T cells express a distinct phenotype and represents a small percentage of the total T cells, persisting for decades. Upon activation, these cells release a cytokine profile characterized by interferon (IFN)-γ and interleukin- (IL)-21 and provide help to B cells to produce antibodies to gluten and tissue transglutaminase (TG2). Moreover, they also control another hallmark of the disease, the infiltration of cytotoxic intraepithelial T CD8 + lymphocytes with activating NK receptors, which recognize stress-induced ligands expressed on epithelial cells and are involved in HLA-DQ2 independent tissue destruction.

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Authors and Affiliations

  1. Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), University of Valladolid-CSIC, Valladolid, Spain

    Eduardo Arranz & José A. Garrote

  2. Servicio de Análisis Clínicos, Hospital Universitario Rio-Hortega de Valladolid, Gerencia Regional de Salud (SACYL), Valladolid, Spain

    José A. Garrote

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  1. Eduardo Arranz
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  2. José A. Garrote
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Correspondence to Eduardo Arranz .

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  1. Department of Pediatrics, São João University Hospital, Porto, Portugal

    Jorge Amil-Dias

  2. Department of Pediatrics, Autonoma University , Madrid, Spain

    Isabel Polanco

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Arranz, E., Garrote, J.A. (2022). Immunopathogenesis of Celiac Disease. In: Amil-Dias, J., Polanco, I. (eds) Advances in Celiac Disease . Springer, Cham. https://doi.org/10.1007/978-3-030-82401-3_4

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  • DOI: https://doi.org/10.1007/978-3-030-82401-3_4

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