Skin dendritic cells induce follicular helper T cells and protective humoral immune responses

Background: The contribution of individual subsets of dendritic cells (DCs) to generation of adaptive immunity is central to understanding immune homeostasis and protective immune responses. Objective: We sought to define functions for steady-state skin DCs. Methods: We present an approach in which we restrict antigen presentation to individual DC subsets in the skin and monitor the effects on endogenous antigen-specific CD4(+) T-and B-cell responses. Results: Presentation of foreign antigen by Langerhans cells (LC) in the absence of exogenous adjuvant led to a large expansion of T follicular helper (T-FH) cells. This was accompanied by B-cell activation, germinal center formation, and protective antibody responses against influenza. The expansion of T-FH cells and antibody responses could be elicited by both systemic and topical skin immunization. T-FH cell induction was not restricted to LCs and occurred in response to antigen presentation by CD103(+) dermal DCs. CD103(+) DCs, despite inducing similar T-FH responses as LCs, were less efficient in induction of germinal center B cells and humoral immune responses. We also found that skin DCs are sufficient to expand CXCR5(+) T-FH cells through an IL-6-and IFN-alpha/beta receptor-independent mechanism, but B cells were required for sustained Bcl-6(+) expression. Conclusions: These data demonstrate that a major unappreciated function of skin DCs is their promotion of T-FH cells and humoral immune responses that potentially represent an efficient approach for vaccination.