title: Regulatory T cells as well as IL-10 are reduced in the skin of patients with dermatitis herpetiformis.
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.
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy. Electronic address: emiliano.antiga@unifi.it.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Antiga
authors.affiliation: Department of Biomedical Sciences and Human Oncology, 1st Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126 Turin, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pierini
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Volpi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139 Florence, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Lami
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bianchi
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Del Bianco
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Renzi
authors.affiliation: Department of Surgery and Translational Medicine, Section of Pathological Anatomy, University of Florence, Viale Morgagni 40, 50139 Florence, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.affiliation: Department of Biomedical Sciences and Human Oncology, 1st Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126 Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Novelli
authors.affiliation: Department of Biomedical Sciences and Human Oncology, 1st Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126 Turin, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Ponti
authors.affiliation: Dermatologic Clinic, St. Maria Hospital, Viale Tristano di Joannuccio 1, 05100 Terni, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Papini
authors.affiliation: Department of Surgery and Translational Medicine, Section of Pathological Anatomy, University of Florence, Viale Morgagni 40, 50139 Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Lollo
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, University of Florence, Viale Morgagni 40, 50139 Florence, Italy.
authors.forename: Antonino Salvatore
authors.initials: AS
authors.lastname: Calabrò
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fabbri
authors.affiliation: Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Caproni
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002446:Celiac Disease / Q000097:blood / Q000276:immunology / Q000378:metabolism; D003874:Dermatitis Herpetiformis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000097:blood / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012867:Skin / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10
keywords: Celiac disease; Dermatitis herpetiformis; Regulatory T cells