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* Mucosal Immunology Section, International Vaccine Institute, Seoul, Republic of Korea;
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;
Biogen Idec, Inc., Cambridge, MA;
Centre d’Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, Parc Scientifique et Technologique de Luminy, Marseille, France.
¶ Yakult Central Institute for Microbiological Research, Tokyo, Japan
Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer’s patch-null mice but abolished in the Peyer’s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin+CD8
– dendritic cells emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin+ cells impaired intestinal IgA Ab responses after TCI. Taken together, these findings suggest that MLN is indispensable for the induction of intestinal IgA Abs following skin immunization and that cross-talk between the skin and gut immune systems might be mediated by langerin+ dendritic cells in the MLN.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the governments of the Republic of Korea, Sweden, Japan, and Kuwait, by a Korean Research Foundation Grant funded by the Korean government (KRF-2005-015-E00117), and by grants from the Ministry of Education, Science, Sports, and Culture and Ministry of Health and Labor in Japan.
2 Address correspondence and reprint requests to Dr. Mi-Na Kweon, Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul, Republic of Korea 151-818. E-mail address: mnkweon{at}ivi.int
3 Abbreviations used in this paper: TCI, transcutaneous immunization; ASC, Ab-secreting cell; BM, bone marrow; CLN, cutaneous lymph node; CT, cholera toxin; CTB, B subunit of CT; DC, dendritic cell; DT, diphtheria toxin; DTR, diphtheria toxin receptor; LC, Langerhans cell; LI, large intestine; LN, lymph node; LTβR, lymphotoxin-β receptor; MLN, mesenteric lymph node; MNC, mononuclear cell; pIgR, polymeric Ig receptor; PP, Peyer’s patch; RA, retinoic acid; SI, small intestine; SIgA, secretory IgA; SP, spleen; TT, tetanus toxoid.
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