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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2019
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.
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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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