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 (TFH) cells. This was accompanied by B-cell activation, germinal center formation, and protective antibody responses against influenza. The expansion of TFH cells and antibody responses could be elicited by both systemic and topical skin immunization. TFH cell induction was not restricted to LCs and occurred in response to antigen presentation by CD103+ dermal DCs. CD103+ DCs, despite inducing similar TFH 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+ TFH cells through an IL-6– and IFN-α/β 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 TFH cells and humoral immune responses that potentially represent an efficient approach for vaccination.
Bibliographical noteFunding Information:
Disclosure of potential conflict of interest: This study was funded by the Dermatology Foundation (00020843), the American Skin Association (00039915), and the National Institutes of Health (AR056632). S. M. Zurawski is employed by the Baylor Health Care System, which has provided discretionary research funding; she holds stock/stock options in Schering Plough Pharmaceuticals and Merck. G. Zurawski is employed by the Baylor Health Care System, which has provided discretionary research funding; he holds stock/stock options in Schering Plough Pharmaceuticals and Merck. D. H. Kaplan and his institution have received funding from the National Institutes of Health (AR056632). B. Z. Igyarto has received funding from the American Skin Association (00039915) and the Dermatology Foundation (00020843). The rest of the authors declare that they have no relevant conflicts of interest.
- Steady-state conditions
- T follicular helper cells
- protective humoral immune responses
- skin dendritic cells