The Emerging Role of Innate Lymphoid Cells (ILCs) and Alarmins in Celiac Disease: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications
Angela Rizzi,
Mario Di Gioacchino,
Luca Gammeri,
Riccardo Inchingolo,
Raffaella Chini,
Francesca Santilli,
Eleonora Nucera,
Sebastiano Gangemi
Affiliations
Angela Rizzi
UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Mario Di Gioacchino
Institute for Clinical Immunotherapy and Advanced Biological Treatments, 65100 Pescara, Italy
Luca Gammeri
Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
Riccardo Inchingolo
Pulmonary Medicine Unit, Department of Neurosciences, Sense Organs and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Raffaella Chini
UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Francesca Santilli
Center for Advanced Studies and Technology, G. d’Annunzio University, 66100 Chieti, Italy
Eleonora Nucera
UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Sebastiano Gangemi
Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
Celiac disease (CD) is an intestinal disease that develops in genetically predisposed individuals and is triggered by the ingestion of gluten. CD was considered a Th1-disease. Today, the role of Th17, IL-21, and IL-17A lymphocytes is well known. Inflammation is regulated by the activity of gluten-specific CD4+ T lymphocytes that produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-21, perpetuating the Th1 response. These cytokines determine an inflammatory state of the small intestine, with consequent epithelial infiltration of lymphocytes and an alteration of the architecture of the duodenal mucosa. B cells produce antibodies against tissue transglutaminase and against deamidated gliadin. Although the role of the adaptive immune response is currently known, the evidence about the role of innate immunity cells is still poorly understood. Epithelial damage determines the release of damage-associated molecular patterns (DAMPs), also known as alarmins. Together with the intestinal epithelial cells and the type 1 innate lymphoid cells (ILC1s), alarmins like TSLP, IL-33, and HMGB1 could have a fundamental role in the genesis and maintenance of inflammation. Our study aims to evaluate the evidence in the literature about the role of ILCs and alarmins in celiac disease, evaluating the possible future diagnostic and therapeutic implications.
