International Immunology, Vol. 14, No. 7, pp. 687-694,
July 2002
© 2002 Japanese Society for Immunology
Pivotal role of CCL25 (TECK)–CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes
1 Department of Molecular Preventive Medicine and Core Research for Evolutional Science and Technology (CREST), Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-033, Japan 2 Department of Hygiene Chemistry, Faculty of Pharmaceutical Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-0826, Japan 3 Department of Microbiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan
Correspondence to: K. Matsushima; E-mail: koujim{at}m.u-tokyo.ac.jp
Transmitting editor: S. Koyasu
Cryptopatches (CP) are murine gut anatomical sites for generating thymus-independent intraepithelial T lymphocytes (IEL). However, it remains elusive how lympho-hematopoietic progenitor cells migrate from bone marrow (BM) into CP and differentiate into IEL. Here we show that mice reconstituted with BM-derived c-kit+ cells express CCL25 (TECK)-intrakine gene, which reduces specifically the chemotactic response to CCL25 but not CXCL12 in the thymocytes. These mice exhibited a dramatic reduction of CP and IEL in the small intestine, and harbored conspicuously decreased numbers of c-kit+ cells in the emaciated CP. In contrast, T cells in the thymic, splenic and lymph node compartments developed normally in these mice. Importantly, it was demonstrated that CD11c+ dendritic stromal cells in CP expressed CCL25 and c-kit+ Lin– BM cells displayed vigorous chemotactic response to CCL25. Furthermore, RT-PCR analysis detects mRNA expression of CCR9 in the c-kit+ Lin– BM cells. Thus, these results demonstrate that the CCL25–CCR9 pathway is essential for CP formation and the consequent appearance of IEL.
Keywords: CCL25, CCR9, cryptopatches, intracellular chemokine, intraepithelial T lymphocytes
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