Skin-Resident Murine Dendritic Cell Subsets Promote Distinct and Opposing Antigen-Specific T Helper Cell Responses

Liu, X. et al., Nature Immunology 12, 416-424 (2011)

Speaker: Yu-Pu Hsia (夏雨璞)                              Time: 13:10~14:00, April 25, 2011

Commentator: Dr. Yee-Shin Lin (林以行老師)    Place: Room 601

Abstract:

Dendritic cells (DCs) are very efficient at activating naïve T cells in vitro and in vivo. They can acquire antigen via multiple routes, and then present processed antigen for CD4⁺ T helper (Th) cells and CD8⁺ cytotoxic T lymphocytes (CTLs), initiating adaptive immune responses [1]. Skin plays an important immunologic role in immune responses to foreign antigens. Three subsets of skin-resident DCs can be distinguished on the basis of anatomical location and cell surface markers, Langerin and CD103 [2]. Langerhans cells (LC) that express Langerin⁺ CD103^- are located in the epidermis and are thus the first APCs to contact pathogens at the skin surface. In the dermis, DC subsets can be segregated into Langerin⁺ CD103⁺ dermal DC (dDC) and Langerin^- CD103⁺ dDC. In vivo, whether these DC subsets have distinct or redundant function remains unclear. In this study, the authors engineered recombinant C. albicans to generate well-characterized immunodominant T cell antigen and developed the cutaneous candidiasis model that does not bypass the epidermis. These tools are helpful to explore the functions of DC subsets. Then they demonstrated thatLangerin⁺ dDC but not LCs are required for cross-presentation of antigen to CTLs in vivo. Direct presentation of antigen by LCs are needed for Th17 development but not for a Th1 cell response. To confirm antigen presentation to LCs, they produced a monoclonal antibody (2G3) that can specifically bind to LCs in vivo, which also showed that LCs are necessary for Th17 cell development. In contrast, the absence of Langerin⁺ dDCs enhanced the Th17 cell response, suggesting that Langerin⁺ dDCs play a suppressive role in Th17 cell development. Thus, skin-resident DC subsets promote distinct and opposing antigen-specific responses in vivo. This research may provide vaccination strategies that selectively target DC populations

in the future.

References:

1.          Banchereau, J. et al.2000. Immunobiology of Dendritic Cells. Annu. Rev. Immunol.18:767-811

2. Kaplan, D.H. 2010. In vivo function of Langerhans cells and dermal dendritic cells. Trends Immunol. 31, 446–451.