Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

Mayer, JU; Hilligan, KL; Chandler, JS; Eccles, DA; Old, SI; Domingues, RG; Yang, J; Webb, GR; Munoz-Erazo, L; Hyde, EJ; Wakelin, KA; Tang, S-C; Chappell, SC; von Daake, S; Brombacher, F; Mackay, CR; Sher, A; Tussiwand, R; Connor, LM; Gallego-Ortega, D; Jankovic, D; Le Gros, G; Hepworth, MR; Lamiable, O; Ronchese, F

Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

Mayer, JU Hilligan, KL Chandler, JS Eccles, DA Old, SI Domingues, RG Yang, J Webb, GR Munoz-Erazo, L Hyde, EJ Wakelin, KA Tang, S-C Chappell, SC von Daake, S Brombacher, F Mackay, CR Sher, A Tussiwand, R Connor, LM Gallego-Ortega, D Jankovic, D Le Gros, G Hepworth, MR Lamiable, O Ronchese, F

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Immunol, 2021, 22, (12), pp. 1538-1550
Issue Date:: 2021-12

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Field	Value	Language
dc.contributor.author	Mayer, JU
dc.contributor.author	Hilligan, KL
dc.contributor.author	Chandler, JS
dc.contributor.author	Eccles, DA
dc.contributor.author	Old, SI
dc.contributor.author	Domingues, RG
dc.contributor.author	Yang, J
dc.contributor.author	Webb, GR
dc.contributor.author	Munoz-Erazo, L
dc.contributor.author	Hyde, EJ
dc.contributor.author	Wakelin, KA
dc.contributor.author	Tang, S-C
dc.contributor.author	Chappell, SC
dc.contributor.author	von Daake, S
dc.contributor.author	Brombacher, F
dc.contributor.author	Mackay, CR
dc.contributor.author	Sher, A
dc.contributor.author	Tussiwand, R
dc.contributor.author	Connor, LM
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Jankovic, D
dc.contributor.author	Le Gros, G
dc.contributor.author	Hepworth, MR
dc.contributor.author	Lamiable, O
dc.contributor.author	Ronchese, F
dc.date.accessioned	2022-04-13T12:18:50Z
dc.date.available	2021-10-05
dc.date.available	2022-04-13T12:18:50Z
dc.date.issued	2021-12
dc.identifier.citation	Nat Immunol, 2021, 22, (12), pp. 1538-1550
dc.identifier.issn	1529-2908
dc.identifier.issn	1529-2916
dc.identifier.uri	http://hdl.handle.net/10453/156211
dc.description.abstract	The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Nat Immunol
dc.relation.isbasedon	10.1038/s41590-021-01067-0
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.mesh	Allergens
dc.subject.mesh	Animals
dc.subject.mesh	CD11b Antigen
dc.subject.mesh	Cell Communication
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Databases, Genetic
dc.subject.mesh	Humans
dc.subject.mesh	Interleukin-13
dc.subject.mesh	Langerhans Cells
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Phenotype
dc.subject.mesh	STAT6 Transcription Factor
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Skin
dc.subject.mesh	Th17 Cells
dc.subject.mesh	Th2 Cells
dc.subject.mesh	Transcriptome
dc.subject.mesh	Langerhans Cells
dc.subject.mesh	Th2 Cells
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Skin
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Humans
dc.subject.mesh	Interleukin-13
dc.subject.mesh	Allergens
dc.subject.mesh	Cell Communication
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Phenotype
dc.subject.mesh	Databases, Genetic
dc.subject.mesh	STAT6 Transcription Factor
dc.subject.mesh	Th17 Cells
dc.subject.mesh	Transcriptome
dc.subject.mesh	CD11b Antigen
dc.title	Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.
dc.type	Journal Article
utslib.citation.volume	22
utslib.location.activity	United States
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
dc.date.updated	2022-04-13T12:18:33Z
pubs.issue	12
pubs.publication-status	Published
pubs.volume	22
utslib.citation.issue	12

Abstract:

The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/156211