2026-08-13T07:18:16Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
Ballester, Alicia
author
Guijarro, Adriana
author
Bravo, Beatriz
author
Hernandez, Javier R
author
Murillas, Rodolfo
author
Gallego, Marta Ines
author
Ballester, Sara
funder
Instituto de Salud Carlos III
2022-04-20T09:57:22Z
2022-04-20T09:57:22Z
2022-03-15
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
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.
eng
Hedgehog
Patched-1
Th lymphocytes
Experimental autoimmune encephalomyelitis
Multiple sclerosis
Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.
research article
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HedgehogSignallingModulatesImmune_2022.pdf.txt