A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.

Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 rece...

Celý popis

Podrobná bibliografie
Hlavní autoři: Salimi, M, Barlow, J, Saunders, S, Xue, L, Gutowska-Owsiak, D, Wang, X, Huang, L, Johnson, D, Scanlon, S, McKenzie, A, Fallon, P, Ogg, G
Médium: Journal article
Jazyk:English
Vydáno: Rockefeller University Press. 2013
_version_ 1826281148195536896
author Salimi, M
Barlow, J
Saunders, S
Xue, L
Gutowska-Owsiak, D
Wang, X
Huang, L
Johnson, D
Scanlon, S
McKenzie, A
Fallon, P
Ogg, G
author_facet Salimi, M
Barlow, J
Saunders, S
Xue, L
Gutowska-Owsiak, D
Wang, X
Huang, L
Johnson, D
Scanlon, S
McKenzie, A
Fallon, P
Ogg, G
author_sort Salimi, M
collection OXFORD
description Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1-/-and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
first_indexed 2024-03-07T00:24:26Z
format Journal article
id oxford-uuid:7da624fe-a335-4eb9-9efd-a1930dfa6d1d
institution University of Oxford
language English
last_indexed 2024-03-07T00:24:26Z
publishDate 2013
publisher Rockefeller University Press.
record_format dspace
spelling oxford-uuid:7da624fe-a335-4eb9-9efd-a1930dfa6d1d2022-03-26T21:05:02ZA role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7da624fe-a335-4eb9-9efd-a1930dfa6d1dEnglishSymplectic Elements at OxfordRockefeller University Press.2013Salimi, MBarlow, JSaunders, SXue, LGutowska-Owsiak, DWang, XHuang, LJohnson, DScanlon, SMcKenzie, AFallon, POgg, GType 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1-/-and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
spellingShingle Salimi, M
Barlow, J
Saunders, S
Xue, L
Gutowska-Owsiak, D
Wang, X
Huang, L
Johnson, D
Scanlon, S
McKenzie, A
Fallon, P
Ogg, G
A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title_full A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title_fullStr A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title_full_unstemmed A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title_short A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
title_sort role for il 25 and il 33 driven type 2 innate lymphoid cells in atopic dermatitis
work_keys_str_mv AT salimim aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT barlowj aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT saunderss aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT xuel aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT gutowskaowsiakd aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT wangx aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT huangl aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT johnsond aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT scanlons aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT mckenziea aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT fallonp aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT oggg aroleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT salimim roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT barlowj roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT saunderss roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT xuel roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT gutowskaowsiakd roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT wangx roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT huangl roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT johnsond roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT scanlons roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT mckenziea roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT fallonp roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis
AT oggg roleforil25andil33driventype2innatelymphoidcellsinatopicdermatitis