Pivotal role of CCL25 (TECK)-CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes.
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.
Onai
Nobuyuki
N
Department of Molecular Preventive Medicine and Core Research for Evolutional Science and Technology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-033, Japan.
Kitabatake
Masahiro
M
Zhang
Yan-yun
YY
Ishikawa
Hiromichi
H
Ishikawa
Sho
S
Matsushima
Kouji
K
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D019743:Chemokines, CXC / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D007107:Immune System / Q000254:growth & development; D007413:Intestinal Mucosa / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014170:Transformation, Genetic
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D054388:Receptors, CCR; D019707:Receptors, Chemokine