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 and M. Cecilia Berin ()
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Leticia Tordesillas: Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai
Daniel Lozano-Ojalvo: Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai
David Dunkin: Pediatric Gastroenterology, Icahn School of Medicine at Mount Sinai
Lucie Mondoulet: DBV Technologies
Judith Agudo: Immunology Institute. Icahn School of Medicine at Mount Sinai
Miriam Merad: Immunology Institute. Icahn School of Medicine at Mount Sinai
Hugh A. Sampson: Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai
M. Cecilia Berin: Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07716-7

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