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oai:repisalud.isciii.es:20.500.12105/141332025-04-10T14:35:58Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19619col_20.500.12105_19617

00925njm 22002777a 4500 dc Ballester, Alicia author Guijarro, Adriana author Bravo, Beatriz author Hernandez, Javier R author Murillas, Rodolfo author Gallego, Marta Ines author Ballester, Sara author 2022-03-15 The Hedgehog (Hh) pathway is essential for the embryonic development and homeostatic maintenance of many adult tissues and organs. It has also been associated with some functions of the innate and adaptive immune system. However, its involvement in the immune response has not been well determined. Here we study the role of Hh signalling in the modulation of the immune response by using the Ptch-1-LacZ+/- mouse model (hereinafter referred to as ptch+/-), in which the hemizygous inactivation of Patched-1, the Hh receptor gene, causes the constitutive activation of Hh response genes. The in vitro TCR stimulation of spleen and lymph node (LN) T cells showed increased levels of Th2 cytokines (IL-4 and IL-10) in ptch+/-cells compared to control cells from wild-type (wt) littermates, suggesting that the Th2 phenotype is favoured by Hh pathway activation. In addition, CD4+ cells secreted less IL-17, and the establishment of the Th1 phenotype was impaired in ptch+/- mice. Consistently, in response to an inflammatory challenge by the induction of experimental autoimmune encephalomyelitis (EAE), ptch+/- mice showed milder clinical scores and more minor spinal cord damage than wt mice. These results demonstrate a role for the Hh/ptch pathway in immune response modulation and highlight the usefulness of the ptch+/- mouse model for the study of T-cell-mediated diseases and for the search for new therapeutic strategies in inflammatory diseases. Int J Mol Sci. 2022;23(6):3171. 10.3390/ijms23063171 1422-0067 International Journal of Molecular Sciences 35328591 http://hdl.handle.net/20.500.12105/14133 Hedgehog Patched-1 Th lymphocytes Experimental autoimmune encephalomyelitis Multiple sclerosis Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.