Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis
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. H...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3171 |
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| author | Alicia Ballester Adriana Guijarro Beatriz Bravo Javier Hernández Rodolfo Murillas Marta I. Gallego Sara Ballester |
| author_facet | Alicia Ballester Adriana Guijarro Beatriz Bravo Javier Hernández Rodolfo Murillas Marta I. Gallego Sara Ballester |
| author_sort | Alicia Ballester |
| collection | DOAJ |
| description | 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<sup>+/−</sup> mouse model (hereinafter referred to as <i>ptch</i><sup>+/−</sup>), 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 <i>ptch</i><sup>+/−</sup>cells compared to control cells from wild-type (wt) littermates, suggesting that the Th2 phenotype is favoured by Hh pathway activation. In addition, CD4<sup>+</sup> cells secreted less IL-17, and the establishment of the Th1 phenotype was impaired in <i>ptch</i><sup>+/−</sup> mice. Consistently, in response to an inflammatory challenge by the induction of experimental autoimmune encephalomyelitis (EAE), <i>ptch</i><sup>+/−</sup> 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 <i>ptch</i><sup>+/−</sup> mouse model for the study of T-cell-mediated diseases and for the search for new therapeutic strategies in inflammatory diseases. |
| first_indexed | 2024-03-09T19:42:22Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:42:22Z |
| publishDate | 2022-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5b7e0340707140a98cb4cef19bd739252023-11-24T01:34:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236317110.3390/ijms23063171Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune EncephalomyelitisAlicia Ballester0Adriana Guijarro1Beatriz Bravo2Javier Hernández3Rodolfo Murillas4Marta I. Gallego5Sara Ballester6Unidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainUnidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainUnidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainUnidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainUnidad de Innovación Biomédica, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Avenida Complutense, 40, 28040 Madrid, SpainUnidad de Histología y Patología mamaria, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainUnidad de Regulación Génica, Unidad Funcional de Investigación en Enfermedades Crónicas, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, SpainThe 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<sup>+/−</sup> mouse model (hereinafter referred to as <i>ptch</i><sup>+/−</sup>), 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 <i>ptch</i><sup>+/−</sup>cells compared to control cells from wild-type (wt) littermates, suggesting that the Th2 phenotype is favoured by Hh pathway activation. In addition, CD4<sup>+</sup> cells secreted less IL-17, and the establishment of the Th1 phenotype was impaired in <i>ptch</i><sup>+/−</sup> mice. Consistently, in response to an inflammatory challenge by the induction of experimental autoimmune encephalomyelitis (EAE), <i>ptch</i><sup>+/−</sup> 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 <i>ptch</i><sup>+/−</sup> mouse model for the study of T-cell-mediated diseases and for the search for new therapeutic strategies in inflammatory diseases.https://www.mdpi.com/1422-0067/23/6/3171HedgehogPatched-1Th lymphocytesexperimental autoimmune encephalomyelitismultiple sclerosis |
| spellingShingle | Alicia Ballester Adriana Guijarro Beatriz Bravo Javier Hernández Rodolfo Murillas Marta I. Gallego Sara Ballester Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis International Journal of Molecular Sciences Hedgehog Patched-1 Th lymphocytes experimental autoimmune encephalomyelitis multiple sclerosis |
| title | Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis |
| title_full | Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis |
| title_fullStr | Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis |
| title_full_unstemmed | Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis |
| title_short | Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis |
| title_sort | hedgehog signalling modulates immune response and protects against experimental autoimmune encephalomyelitis |
| topic | Hedgehog Patched-1 Th lymphocytes experimental autoimmune encephalomyelitis multiple sclerosis |
| url | https://www.mdpi.com/1422-0067/23/6/3171 |
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