Skin-resident dendritic cells (DCs) are well positioned to encounter cutaneous pathogens and are required for the initiation of adaptive immune responses. There are at least three subsets of skin DC- Langerhans cells (LC), Langerin+ dermal DCs (dDCs), and classic dDCs. Whether these subsets have distinct or redundant function in vivo is poorly understood. Using a Candida albicans skin infection model, we have shown that direct presentation of antigen by LC is necessary and sufficient for the generation of antigen-specific T helper-17 (Th17) cells but not for the generation of cytotoxic lymphocytes (CTLs). In contrast, Langerin+ dDCs are required for the generation of antigen specific CTL and Th1 cells. Langerin+ dDCs also inhibited the ability of LCs and classic DCs to promote Th17 cell responses. This work demonstrates that skin-resident DC subsets promote distinct and opposing antigen-specific responses.
Bibliographical noteFunding Information:
S.Z. and G.Z. are inventors on patent applications for LC-targeting vaccines. We would like to acknowledge K. Hogquist and M. Jenkins for their insightful input and critique of the manuscript. We thank the University of Minnesota Research Animal Resources staff for animal care. P. Champoux and the Flow Cytometry Core Facility at the Center for Immunology (University of Minnesota) assisted with sorting and flow-cytometry experiments. This work was supported by a grant from the National Institutes of Health (NIH) (R01-AR056632) to D.H.K., a Dermatology Foundation research award (BZI), and an American Skin Association research award (BZI). D.H.K. is also supported by the Al Zelickson endowed professorship. The 2G3 antibody reagents were developed with the support of NIH grant U19 AI057234 and the Baylor Health Care System Foundation. B.T.E. is the recipient of a Burroughs Wellcome Fund Career Award for Medical Scientists.
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