Rodríguez-Jiménez, PedroFernández Messina, Lola MaríaOvejero-Benito, MaríaChicharro, PabloVera-Tomé, PaulaVara, AliciaCibrian, DanayMartínez-Fleta, PedroJiménez-Fernández, MaríaSánchez-García, InésLlamas-Velasco, MarAbad-Santos, FranciscoSánchez-Madrid, FranciscoDauden, EstebanFuente, Hortensia de la2024-01-312024-01-312021Rodríguez-Jiménez, P., Fernández-Messina, L., Ovejero-Benito, M.C. et al. Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis. Sci Rep 11, 14579 (2021). https://doi.org/10.1038/s41598-021-93780-x10.1038/s41598-021-93780-xhttps://hdl.handle.net/20.500.14352/97235Acknowledgements Instituto de Salud Carlos III (AES 2017): PI17/01972 to E.D. Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. This research has been co-financed by Fondo Europeo de Desarrollo Regional (FEDER).The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2045-2322https://doi.org/10.1038/s41598-021-93780-xhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285512/open access612.017GADD45 proteinsPsoriasisImmune responsesBiología molecular (Biología)Biología celular (Biología)Bioquímica (Biología)Inmunología2407 Biología Celular2412 Inmunología2403 Bioquímica2415 Biología Molecular