Skin dendritic cells induce follicular helper T cells and protective humoral immune responses (VAC4P.1101)

Skin-resident dendritic cells (DC) play a crucial role in initiation of adaptive immune responses against cutaneous pathogens as well as in the maintenance of peripheral tolerance. Recent studies have suggested that steady-state Langerhans cells (LC) induce regulatory T cells against self-antigens. However, the immune response induced by skin DC against foreign antigen in the absence of adjuvants has not been addressed. Here we report that, using anti-huLangerin/ muLangerin antibodies, we could specifically target antigens to LC or CD103+ dermal DC. Presentation of the foreign peptide 2W1S by either LC or CD103+ dDC was sufficient for expansion of naïve CD4+ T cells and induction of T follicular helper cell (Tfh) differentiation. Notably, topical application of peptide or protein also efficiently induced Tfh. The expansion of Tfh specific to foreign peptide was accompanied by activation and expansion of antigen-specific B cells and the development of a robust antibody response that provided systemic protection against influenza infection. This study not only reveals a major unappreciated function of skin DC in humoral response, but also provides insight into DC-targeted vaccine design.