PDL2+ CD11b+ dermal dendritic cells capture topical antigen through hair follicles to prime LAP+ Tregs

Leticia Tordesillas; Daniel Lozano-Ojalvo; David Dunkin; Lucie Mondoulet; Judith Agudo; Miriam Merad; Hugh A. Sampson; M. Cecilia Berin

doi:10.1038/s41467-018-07716-7

PDL2⁺ CD11b⁺ dermal dendritic cells capture topical antigen through hair follicles to prime LAP⁺ Tregs

Leticia Tordesillas, Daniel Lozano-Ojalvo, David Dunkin, Lucie Mondoulet, Judith Agudo, Miriam Merad, Hugh A. Sampson, M. Cecilia Berin^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

The skin immune system must discriminate between innocuous antigens and pathogens. Antigen applied topically using a Viaskin® patch elicits immune tolerance that can suppress colitis and food allergy. Here we show how topical antigen is acquired and presented by dendritic cells in the skin. Topical antigen is acquired by Langerhans cells (LC) and CD11b⁺ cDC2s but not cDC1s, and both LCs and CD11b⁺ cDC2s reaching the lymph node can prime T cells and expand LAP⁺ Tregs. However, LCs are neither required nor sufficient for T cell priming, and have no role in tolerance induction. Conversely, IRF-4-dependent cDC2s are required for T cell priming. Acquisition of antigen in the dermis, delivery to the draining lymph node, and generation of tolerance are all absent in hairless mice. These results indicate an important function for hair follicle niche and CD11b⁺ cDC2s in antigen acquisition, and in generation of primary immune tolerance to topical antigens.

Original language	English (US)
Article number	5238
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07716-7
State	Published - Dec 1 2018

Funding

We thank the Microscopy Core at Icahn School of Medicine at Mount Sinai, in particular Dr. Nikos Tzavaras, for assistance with confocal experiments and the Flow Cytometry Core for assistance with cell sorting. We also thank the NIH Tetramer Core Facility for providing the I-A(b) OVA323-337 tetramer. Financial support for the study was provided by NIH grants AI093577, AI124062 (to M.C.B.), K08DK102978 (to D.D.), the Robin Chemers Postdoctoral Fellowship (to L.T.), and a postdoctoral fellowship from the Spanish Fundación Alfonso Martín Escudero (to D.L.O.).

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-018-07716-7

Cite this

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title = "PDL2+ CD11b+ dermal dendritic cells capture topical antigen through hair follicles to prime LAP+ Tregs",

abstract = "The skin immune system must discriminate between innocuous antigens and pathogens. Antigen applied topically using a Viaskin{\textregistered} patch elicits immune tolerance that can suppress colitis and food allergy. Here we show how topical antigen is acquired and presented by dendritic cells in the skin. Topical antigen is acquired by Langerhans cells (LC) and CD11b+ cDC2s but not cDC1s, and both LCs and CD11b+ cDC2s reaching the lymph node can prime T cells and expand LAP+ Tregs. However, LCs are neither required nor sufficient for T cell priming, and have no role in tolerance induction. Conversely, IRF-4-dependent cDC2s are required for T cell priming. Acquisition of antigen in the dermis, delivery to the draining lymph node, and generation of tolerance are all absent in hairless mice. These results indicate an important function for hair follicle niche and CD11b+ cDC2s in antigen acquisition, and in generation of primary immune tolerance to topical antigens.",

author = "Leticia Tordesillas and Daniel Lozano-Ojalvo and David Dunkin and Lucie Mondoulet and Judith Agudo and Miriam Merad and Sampson, {Hugh A.} and Berin, {M. Cecilia}",

note = "Funding Information: We thank the Microscopy Core at Icahn School of Medicine at Mount Sinai, in particular Dr. Nikos Tzavaras, for assistance with confocal experiments and the Flow Cytometry Core for assistance with cell sorting. We also thank the NIH Tetramer Core Facility for providing the I-A(b) OVA323-337 tetramer. Financial support for the study was provided by NIH grants AI093577, AI124062 (to M.C.B.), K08DK102978 (to D.D.), the Robin Chemers Postdoctoral Fellowship (to L.T.), and a postdoctoral fellowship from the Spanish Fundaci{\'o}n Alfonso Mart{\'i}n Escudero (to D.L.O.). Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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AU - Mondoulet, Lucie

AU - Agudo, Judith

AU - Merad, Miriam

AU - Sampson, Hugh A.

AU - Berin, M. Cecilia

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N2 - The skin immune system must discriminate between innocuous antigens and pathogens. Antigen applied topically using a Viaskin® patch elicits immune tolerance that can suppress colitis and food allergy. Here we show how topical antigen is acquired and presented by dendritic cells in the skin. Topical antigen is acquired by Langerhans cells (LC) and CD11b+ cDC2s but not cDC1s, and both LCs and CD11b+ cDC2s reaching the lymph node can prime T cells and expand LAP+ Tregs. However, LCs are neither required nor sufficient for T cell priming, and have no role in tolerance induction. Conversely, IRF-4-dependent cDC2s are required for T cell priming. Acquisition of antigen in the dermis, delivery to the draining lymph node, and generation of tolerance are all absent in hairless mice. These results indicate an important function for hair follicle niche and CD11b+ cDC2s in antigen acquisition, and in generation of primary immune tolerance to topical antigens.

AB - The skin immune system must discriminate between innocuous antigens and pathogens. Antigen applied topically using a Viaskin® patch elicits immune tolerance that can suppress colitis and food allergy. Here we show how topical antigen is acquired and presented by dendritic cells in the skin. Topical antigen is acquired by Langerhans cells (LC) and CD11b+ cDC2s but not cDC1s, and both LCs and CD11b+ cDC2s reaching the lymph node can prime T cells and expand LAP+ Tregs. However, LCs are neither required nor sufficient for T cell priming, and have no role in tolerance induction. Conversely, IRF-4-dependent cDC2s are required for T cell priming. Acquisition of antigen in the dermis, delivery to the draining lymph node, and generation of tolerance are all absent in hairless mice. These results indicate an important function for hair follicle niche and CD11b+ cDC2s in antigen acquisition, and in generation of primary immune tolerance to topical antigens.

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