Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses

Immunity. 2011 Aug 26;35(2):260-72. doi: 10.1016/j.immuni.2011.06.005. Epub 2011 Jul 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Surface / biosynthesis
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Candida albicans / immunology*
  • Candida albicans / pathogenicity
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Candidiasis / pathology
  • Cells, Cultured
  • Cross-Priming
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Lectins, C-Type / biosynthesis
  • Lymphocyte Activation
  • Mannose-Binding Lectins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Repressor Proteins / genetics
  • Skin / microbiology
  • Skin / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / microbiology
  • T-Lymphocyte Subsets / parasitology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Th17 Cells / microbiology
  • Th17 Cells / pathology

Substances

  • Antigens, Bacterial
  • Antigens, Surface
  • Basic-Leucine Zipper Transcription Factors
  • Cd207 protein, mouse
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Repressor Proteins
  • SNFT protein, mouse