AUTHOR=Caproni Marzia , Capone Manuela , Rossi Maria Caterina , Santarlasci Veronica , Maggi Laura , Mazzoni Alessio , Rossettini Beatrice , Renzi Daniela , Quintarelli Lavinia , Bianchi Beatrice , Ninci Alessandra , Lami Gabriele , Calabrò Antonio , Cosmi Lorenzo , Annunziato Francesco , Liotta Francesco TITLE=T Cell Response Toward Tissue-and Epidermal-Transglutaminases in Coeliac Disease Patients Developing Dermatitis Herpetiformis JOURNAL=Frontiers in Immunology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.645143 DOI=10.3389/fimmu.2021.645143 ISSN=1664-3224 ABSTRACT=The reason why only few coeliac patients develop the cutaneous manifestation named dermatitis herpetiformis (DH) is still unknown. Epidermal transglutaminase (TG3) has been described as the main autoantigen of humoral immunity in DH but the mechanisms leading to this autoimmune response remain obscure. Here we characterized T cells from skin, gut and peripheral blood of DH and coeliac disease (CD) patients, evaluated the impact of the gluten-free diet (GFD) on circulating T lymphocytes' phenotype and investigated antigen specific T cell response towards epidermal and tissue transglutaminase (TG2). DH patients showed an increased frequency of skin-derived T cells producing TNFα when compared to CD patients. Moreover, circulating T cells producing TNFα and IL-17A positively correlated with clinical score of skin disease activity and decreased after GFD. Finally, TG2 and TG3-specific T cells resulted more reactive to antigens stimulation in DH patients and showed cross reactivity towards the two autoantigens in both the group of patients.