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.
Highlights
The skin immune system must discriminate between innocuous antigens and pathogens
To determine how antigen applied topically to healthy skin is acquired and presented by skin dendritic cell subsets (DCs) subsets to generate LAP+ Tregs, here we show that Langerhans cells (LC) and CD11b+ cDC2s acquire and present topical antigen to T cells, but only cDC2s are required for T cell priming
Topical antigen is transported by CD11b+ cDC2s and LCs
Summary
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. CDC1 and cDC2 subsets in the skin can be loosely divided based on expression of CD103 and CD11b, respectively, there is a population of CD103−CD11b− DCs that are IRF4 dependent. Topical application of antigen generated antigen-specific LAP+ Foxp3− Tregs that expressed CCR9 and CCR6 to support intestinal homing, and suppressed T cell and mast cell activation through TGFβ dependent mechanisms[4,5]. These cells are similar in phenotype to Th3 cells identified as playing a critical role in the development of oral tolerance[19,20,21]. Antigen acquisition and generation of tolerance are absent in hairless mice, suggesting a key role of hair follicle niche in delivery of topical antigen to skin DCs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
