International Immunology, Vol. 13, No. 5, 695-704,
May 2001
© 2001 Japanese Society for Immunology
Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-ß1-dependent cells
1 Department of Immunology, School of Life Science, and
2 Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
3 Second Department of Pathology, Niigata University School of Medicine, Niigata 951-8510, Japan
4 Laboratory of Immunobiology, Graduate School of Science,
5 Graduate School of Biostudies and
6 Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8502, Japan
7 Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA
8 Department of Internal Medicine, Health Science University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan
9 Department of Hygiene, Gifu University, School of Medicine, Gifu 500-8705, Japan
Correspondence to: S.-I. Hayashi
Antigen capturing in the skin and antigen trafficking into regional lymph nodes (LN) initiate immune responses. In this study, employing melanin granule (MG) as an easily traceable antigen in two mouse strains that carried steel factor or hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in the dermis respectively, we investigated the mechanism of antigen trafficking from the skin. MG captured in the epidermis or dermis accumulated in the regional LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass through the lymphatics and reached many tissues. Since inflammatory regions were not observed in the skin of either type of transgenic mouse, our developmental system enables us to investigate constitutive capturing and trafficking of insoluble antigens in the steady state. Both dendritic cells and macrophages were laden with MG in the regional LN. To determine which cells traffic antigens to the LN, we prepared double mutants that carried the transgenes and lacked transforming growth factor (TGF)-ß1, since mice lacking TGF-ß1 are reported to be deficient of Langerhans cells. Few MG were observed in the regional LN of these double-mutant mice. We also showed that signaling via macrophage colony stimulating factor receptor or Flt3/Flk2 is not essential for development of the cells for this antigen trafficking. These results indicate that antigens in the epidermis and dermis in the steady state are trafficked into regional LN only by TGF-ß1-dependent cells, which may be a dendritic cell lineage.
Keywords: autoantigen, dendritic cell, hepatocyte growth factor (Hgf), Langerhans cell, melanin granule, steel factor (Mgf)
10 Present address: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan
Transmitting editor: K. Takatsu
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