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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® 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.

SUBMITTER: Tordesillas L

PROVIDER: S-EPMC6286332 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Tordesillas Leticia L Lozano-Ojalvo Daniel D Dunkin David D Mondoulet Lucie L Agudo Judith J Merad Miriam M Sampson Hugh A HA Berin M Cecilia MC

Nature communications 20181207 1

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+ T ...[more]

PMID: 30531969

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Project description:PURPOSE:Telogen (resting phase) hair follicles (HFs) are more radioresistant than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18 is strongly expressed in telogen HFs to maintain the telogen phase, whereas several other FGFs exert radioprotective effects; however, the role of FGF18 in the radioresistance of HFs remains unknown. This study focused on clarifying the role of FGF18 in the radioresistance of telogen HFs and its potential as a radioprotector. METHODS AND MATERIALS:BALB/c mice with telogen or plucking-induced anagen HFs were exposed to total body irradiation with ?-rays at 4 to 12 Gy after intraperitoneal treatment with FGF18 or an FGF receptor inhibitor. A time course analysis was performed histologically and hair growth was observed 14 or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and Western blotting. RESULTS:Telogen irradiation at 6 Gy resulted in transient cell growth arrest, leading to successful hair growth, whereas anagen irradiation failed to promote hair growth. Telogen irradiation did not induce apoptosis in HFs or reduce HF stem cells, whereas anagen irradiation induced apoptosis and reduced stem cell numbers. The Inhibition of FGF receptor signaling during the telogen phase promoted HF cell proliferation; however, hair failed to grow after irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest after anagen irradiation with enhanced DNA repair, leading to the inhibition of apoptosis, maintenance of HF stem cells, and successful hair growth. Moreover, FGF18 reduced the expression levels of genes promoting G2/M transition as well as the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M arrest in the keratinocyte cell line HaCaT. CONCLUSIONS:These results suggest that FGF18 signaling mediates radioresistance in telogen HFs by arresting the cell cycle, and that FGF18 has potential as a radioprotector for radiation-induced alopecia.

Dataset Information

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

Publications

PDL2<sup>+</sup> CD11b<sup>+</sup> dermal dendritic cells capture topical antigen through hair follicles to prime LAP<sup>+</sup> Tregs.

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