Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes.
CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in double- and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development. It was noted that there was only a one-day lag in the appearance of double-positive cells during fetal ontogeny in CCR9(-/-) thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9(-/-) mice failed to respond to TECK/CCL25. Taken together, these results suggest that in thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25, and that it is dispensable for proper T-cell development. Bone marrow pre-pro-B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pre-pro-B cells in CCR9(-/-) mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell-to-epithelial cell ratio is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor gammadelta(+) compartment.
Wurbel
M A
MA
Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS- Universite de la Mediterranee, Campus de Luminy, Marseille, France.
Malissen
M
M
Guy-Grand
D
D
Meffre
E
E
Nussenzweig
M C
MC
Richelme
M
M
Carrier
A
A
Malissen
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005333:Fetus; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects*; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054388:Receptors, CCR; D019707:Receptors, Chemokine