Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation
Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668675/ https://www.ncbi.nlm.nih.gov/pubmed/31264977 http://dx.doi.org/10.1172/JCI125170 |
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author | Papaioannou, Eleftheria Yánez, Diana C. Ross, Susan Lau, Ching-In Solanki, Anisha Chawda, Mira Manilal Virasami, Alex Ranz, Ismael Ono, Masahiro O’Shaughnessy, Ryan F. L. Crompton, Tessa |
author_facet | Papaioannou, Eleftheria Yánez, Diana C. Ross, Susan Lau, Ching-In Solanki, Anisha Chawda, Mira Manilal Virasami, Alex Ranz, Ismael Ono, Masahiro O’Shaughnessy, Ryan F. L. Crompton, Tessa |
author_sort | Papaioannou, Eleftheria |
collection | PubMed |
description | Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and the levels of Shh expression determined disease severity. Hh-mediated transcription in skin T cells in AD-induced mice increased Treg populations and their suppressive function through increased active transforming growth factor–β (TGF-β) in Treg signaling to skin T effector populations to reduce disease progression and pathology. RNA sequencing of skin CD4(+) T cells from AD-induced mice demonstrated that Hh signaling increased expression of immunoregulatory genes and reduced expression of inflammatory and chemokine genes. Addition of recombinant Shh to cultures of naive human CD4(+) T cells in iTreg culture conditions increased FOXP3 expression. Our findings establish an important role for Shh upregulation in preventing AD, by increased Gli-driven, Treg cell–mediated immune suppression, paving the way for a potential new therapeutic strategy. |
format | Online Article Text |
id | pubmed-6668675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-66686752019-08-02 Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation Papaioannou, Eleftheria Yánez, Diana C. Ross, Susan Lau, Ching-In Solanki, Anisha Chawda, Mira Manilal Virasami, Alex Ranz, Ismael Ono, Masahiro O’Shaughnessy, Ryan F. L. Crompton, Tessa J Clin Invest Research Article Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and the levels of Shh expression determined disease severity. Hh-mediated transcription in skin T cells in AD-induced mice increased Treg populations and their suppressive function through increased active transforming growth factor–β (TGF-β) in Treg signaling to skin T effector populations to reduce disease progression and pathology. RNA sequencing of skin CD4(+) T cells from AD-induced mice demonstrated that Hh signaling increased expression of immunoregulatory genes and reduced expression of inflammatory and chemokine genes. Addition of recombinant Shh to cultures of naive human CD4(+) T cells in iTreg culture conditions increased FOXP3 expression. Our findings establish an important role for Shh upregulation in preventing AD, by increased Gli-driven, Treg cell–mediated immune suppression, paving the way for a potential new therapeutic strategy. American Society for Clinical Investigation 2019-07-02 2019-08-01 /pmc/articles/PMC6668675/ /pubmed/31264977 http://dx.doi.org/10.1172/JCI125170 Text en © 2019 Papaioannou et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Papaioannou, Eleftheria Yánez, Diana C. Ross, Susan Lau, Ching-In Solanki, Anisha Chawda, Mira Manilal Virasami, Alex Ranz, Ismael Ono, Masahiro O’Shaughnessy, Ryan F. L. Crompton, Tessa Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title | Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title_full | Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title_fullStr | Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title_full_unstemmed | Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title_short | Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation |
title_sort | sonic hedgehog signaling limits atopic dermatitis via gli2-driven immune regulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668675/ https://www.ncbi.nlm.nih.gov/pubmed/31264977 http://dx.doi.org/10.1172/JCI125170 |
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