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Article

Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis

1
Unidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain
2
Unidad de Innovación Biomédica, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Avenida Complutense, 40, 28040 Madrid, Spain
3
Unidad de Histología y Patología mamaria, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editors: Maxime Jacquet, Bruno Bonetti and Jeongho Park
Int. J. Mol. Sci. 2022, 23(6), 3171; https://doi.org/10.3390/ijms23063171
Received: 19 February 2022 / Revised: 9 March 2022 / Accepted: 11 March 2022 / Published: 15 March 2022
(This article belongs to the Special Issue Immune Cell Regulation during Inflammatory Responses)
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. View Full-Text
Keywords: Hedgehog; Patched-1; Th lymphocytes; experimental autoimmune encephalomyelitis; multiple sclerosis Hedgehog; Patched-1; Th lymphocytes; experimental autoimmune encephalomyelitis; multiple sclerosis
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MDPI and ACS Style

Ballester, A.; Guijarro, A.; Bravo, B.; Hernández, J.; Murillas, R.; Gallego, M.I.; Ballester, S. Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis. Int. J. Mol. Sci. 2022, 23, 3171. https://doi.org/10.3390/ijms23063171

AMA Style

Ballester A, Guijarro A, Bravo B, Hernández J, Murillas R, Gallego MI, Ballester S. Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis. International Journal of Molecular Sciences. 2022; 23(6):3171. https://doi.org/10.3390/ijms23063171

Chicago/Turabian Style

Ballester, Alicia, Adriana Guijarro, Beatriz Bravo, Javier Hernández, Rodolfo Murillas, Marta I. Gallego, and Sara Ballester. 2022. "Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis" International Journal of Molecular Sciences 23, no. 6: 3171. https://doi.org/10.3390/ijms23063171

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