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
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Holcmann, P. Stoitzner, B. Drobits, P. Luehrs, G. Stingl, N. Romani, D. Maurer, and M. Sibilia Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen J. Immunol., July 15, 2009; 183(2): 1133 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Bursch, B. E. Rich, and K. A. Hogquist Langerhans Cells Are Not Required for the CD8 T Cell Response to Epidermal Self-Antigens J. Immunol., April 15, 2009; 182(8): 4657 - 4664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jakubzick, M. Bogunovic, A. J. Bonito, E. L. Kuan, M. Merad, and G. J. Randolph Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes J. Exp. Med., November 24, 2008; 205(12): 2839 - 2850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. A. M. Santegoets, S. Gibbs, K. Kroeze, R. van de Ven, R. J. Scheper, C. A. Borrebaeck, T. D. de Gruijl, and M. Lindstedt Transcriptional profiling of human skin-resident Langerhans cells and CD1a+ dermal dendritic cells: differential activation states suggest distinct functions J. Leukoc. Biol., July 1, 2008; 84(1): 143 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, L. S. Bursch, A. Kissenpfennig, B. Malissen, S. C. Jameson, and K. A. Hogquist Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions J. Immunol., April 1, 2008; 180(7): 4722 - 4727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bohannon, W. Cui, R. Cox, R. Przkora, E. Sherwood, and T. Toliver-Kinsky Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection J. Immunol., March 1, 2008; 180(5): 3038 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-H. Hovav, M. W. Panas, S. Rahman, P. Sircar, G. Gillard, M. J. Cayabyab, and N. L. Letvin Duration of Antigen Expression In Vivo following DNA Immunization Modifies the Magnitude, Contraction, and Secondary Responses of CD8+ T Lymphocytes J. Immunol., November 15, 2007; 179(10): 6725 - 6733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Kaplan, M. O. Li, M. C. Jenison, W. D. Shlomchik, R. A. Flavell, and M. J. Shlomchik Autocrine/paracrine TGF{beta}1 is required for the development of epidermal Langerhans cells J. Exp. Med., October 29, 2007; 204(11): 2545 - 2552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Nichols, Y. Chen, T. A. Colella, C. L. Bennett, B. E. Clausen, and V. H. Engelhard Deletional Self-Tolerance to a Melanocyte/Melanoma Antigen Derived from Tyrosinase Is Mediated by a Radio-Resistant Cell in Peripheral and Mesenteric Lymph Nodes J. Immunol., July 15, 2007; 179(2): 993 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Obayashi, T. Doi, and S. Koyasu Dendritic cells suppress IgE production in B cells Int. Immunol., February 1, 2007; 19(2): 217 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Braun, L. Galibert, T. Nakajima, H. Saito, V. V. Quang, M. Rubio, and M. Sarfati Semimature Stage: A Checkpoint in a Dendritic Cell Maturation Program That Allows for Functional Reversion after Signal-Regulatory Protein-{alpha} Ligation and Maturation Signals J. Immunol., December 15, 2006; 177(12): 8550 - 8559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yoshino, H. Yamazaki, L. D. Shultz, and S.-I. Hayashi Constant rate of steady-state self-antigen trafficking from skin to regional lymph nodes Int. Immunol., November 1, 2006; 18(11): 1541 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Durakovic, K. B. Bezak, M. Skarica, V. Radojcic, E. J. Fuchs, G. F. Murphy, and L. Luznik Host-Derived Langerhans Cells Persist after MHC-Matched Allografting Independent of Donor T Cells and Critically Influence the Alloresponses Mediated by Donor Lymphocyte Infusions J. Immunol., October 1, 2006; 177(7): 4414 - 4425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J A Hardin Dendritic cells: potential triggers of autoimmunity and targets for therapy Ann Rheum Dis, November 1, 2005; 64(suppl_4): iv86 - iv90. [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Bennett, E. van Rijn, S. Jung, K. Inaba, R. M. Steinman, M. L. Kapsenberg, and B. E. Clausen Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity J. Cell Biol., May 23, 2005; 169(4): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chang-Rodriguez, W. Hoetzenecker, C. Schwarzler, T. Biedermann, S. Saeland, and A. Elbe-Burger Fetal and neonatal murine skin harbors Langerhans cell precursors J. Leukoc. Biol., March 1, 2005; 77(3): 352 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ota, M. Aoki-Ota, K. Tsunoda, K. Simoda, T. Nishikawa, M. Amagai, and S. Koyasu Auto-reactive B cells against peripheral antigen, desmoglein 3, escape from tolerance mechanism Int. Immunol., October 1, 2004; 16(10): 1487 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Apostolou and H. von Boehmer In Vivo Instruction of Suppressor Commitment in Naive T Cells J. Exp. Med., May 17, 2004; 199(10): 1401 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takahashi, K. Kurosaka, and Y. Kobayashi Immature dendritic cells reduce proinflammatory cytokine production by a coculture of macrophages and apoptotic cells in a cell-to-cell contact-dependent manner J. Leukoc. Biol., May 1, 2004; 75(5): 865 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Mullins, S. L. Sheasley, R. M. Ream, T. N.J. Bullock, Y.-X. Fu, and V. H. Engelhard Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control J. Exp. Med., October 6, 2003; 198(7): 1023 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Allan, C. M. Smith, G. T. Belz, A. L. van Lint, L. M. Wakim, W. R. Heath, and F. R. Carbone Epidermal Viral Immunity Induced by CD8{alpha}+ Dendritic Cells But Not by Langerhans Cells Science, September 26, 2003; 301(5641): 1925 - 1928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yoshino, H. Yamazaki, H. Nakano, T. Kakiuchi, K. Ryoke, T. Kunisada, and S.-I. Hayashi Distinct antigen trafficking from skin in the steady and active states Int. Immunol., June 1, 2003; 15(6): 773 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Geissmann, M.C. Dieu-Nosjean, C. Dezutter, J. Valladeau, S. Kayal, M. Leborgne, N. Brousse, S. Saeland, and J. Davoust Accumulation of Immature Langerhans Cells in Human Lymph Nodes Draining Chronically Inflamed Skin J. Exp. Med., August 19, 2002; 196(4): 417 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Randolph, G. Sanchez-Schmitz, R. M. Liebman, and K. Schakel The CD16+ (Fc{gamma}RIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting J. Exp. Med., August 19, 2002; 196(4): 517 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takahara, Y. Omatsu, Y. Yashima, Y. Maeda, S. Tanaka, T. Iyoda, B. Clusen, K. Matsubara, J. Letterio, R. M. Steinman, et al. Identification and expression of mouse Langerin (CD207) in dendritic cells Int. Immunol., May 1, 2002; 14(5): 433 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Steinman and M. C. Nussenzweig Inaugural Article: Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance PNAS, January 8, 2002; 99(1): 351 - 358. [Abstract] [Full Text] [PDF]
|
|