Emiliano Antiga1, Pietro Quaglino2, Ilaria Pierini3, Walter Volpi3, Gabriele Lami4, Beatrice Bianchi3, Elena Del Bianco3, Daniela Renzi4, Gianna Baroni5, Mauro Novelli2, Renata Ponti2, Manuela Papini6, Simonetta Di Lollo5, Antonino Salvatore Calabrò4, Paolo Fabbri3, Marzia Caproni3. 1. Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy. Electronic address: emiliano.antiga@unifi.it. 2. Department of Biomedical Sciences and Human Oncology, 1st Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126 Turin, Italy. 3. Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy. 4. Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139 Florence, Italy. 5. Department of Surgery and Translational Medicine, Section of Pathological Anatomy, University of Florence, Viale Morgagni 40, 50139 Florence, Italy. 6. Dermatologic Clinic, St. Maria Hospital, Viale Tristano di Joannuccio 1, 05100 Terni, Italy.
Abstract
BACKGROUND: Dermatitis herpetiformis (DH) and celiac disease (CD) are considered as autoimmune diseases that share a defined trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not fully understood and no data are available about the immune regulation in such a disease. OBJECTIVE: The aim of this study was to assess if alterations in the pattern of the immune response and, in particular, impairments of regulatory T (Tregs) cells may contribute to the phenotypic differences between DH and CD. METHODS: We investigated the presence of Tregs cell markers, in the skin, the duodenum and the blood of patients with DH by immunohistochemistry, confocal microscopy and flow cytometry. As controls, we included patients with bullous pemphigoid, patients with CD without skin lesions, as well as healthy subjects (HS). RESULTS: In the skin of DH patient, we found a significantly lower proportion of FOXP3(+) Tregs and IL-10(+) cells than in HS (p < 0.001 for both cell populations). In duodenal samples, no differences where found in the proportion of Tregs between patients with DH and patients with CD without skin manifestations. Finally, the frequency of CD25(bright)FOXP3(+) cells within the CD4(+) subset was significantly reduced in CD patients either with or without DH with respect to HS (p = 0.029 and p = 0.017, respectively). CONCLUSIONS: Our findings suggested that a reduction of Tregs may play a major role in the skin, leading to a defective suppressive function and thus to the development of the lesions. By contrast, no differences could be detected about Tregs between patients with DH and patients with CD in the duodenum, suggesting that the mechanisms of the intestinal damage are similar in both diseases.
BACKGROUND:Dermatitis herpetiformis (DH) and celiac disease (CD) are considered as autoimmune diseases that share a defined trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not fully understood and no data are available about the immune regulation in such a disease. OBJECTIVE: The aim of this study was to assess if alterations in the pattern of the immune response and, in particular, impairments of regulatory T (Tregs) cells may contribute to the phenotypic differences between DH and CD. METHODS: We investigated the presence of Tregs cell markers, in the skin, the duodenum and the blood of patients with DH by immunohistochemistry, confocal microscopy and flow cytometry. As controls, we included patients with bullous pemphigoid, patients with CD without skin lesions, as well as healthy subjects (HS). RESULTS: In the skin of DHpatient, we found a significantly lower proportion of FOXP3(+) Tregs and IL-10(+) cells than in HS (p < 0.001 for both cell populations). In duodenal samples, no differences where found in the proportion of Tregs between patients with DH and patients with CD without skin manifestations. Finally, the frequency of CD25(bright)FOXP3(+) cells within the CD4(+) subset was significantly reduced in CDpatients either with or without DH with respect to HS (p = 0.029 and p = 0.017, respectively). CONCLUSIONS: Our findings suggested that a reduction of Tregs may play a major role in the skin, leading to a defective suppressive function and thus to the development of the lesions. By contrast, no differences could be detected about Tregs between patients with DH and patients with CD in the duodenum, suggesting that the mechanisms of the intestinal damage are similar in both diseases.