Effect of reduced EPHB4 expression in thymic epithelial cells on thymocyte development and peripheral T cell function.
The Eph kinase (EPH) and ephrin (EFN) families are involved in a broad range of developmental processes. Increasing evidence is demonstrating the important roles of EPHBs and EphrinBs in the immune system. In this study on epithelial cell-specific Ephb4 knockout (KO) mice, we investigated T-cell development and function after EPHB4 deletion. KO mice presented normal thymic weight and cellularity. Their thymocyte subpopulation percentages were in the normal range. KO mice had normal T-cell numbers and percentages in the spleen, and T cells were activated and proliferated normally upon TCR ligation. Furthermore, naïve spleen CD4 cells from KO and wild type mice were capable of differentiating, in a comparable manner, into Th1, Th17 and Treg cells. In vivo, KO mice mounted effective delayed type hypersensitivity responses, indicating that thymocytes develop normally in the absence of TEC EPHB4, and T cells derived from EPHB4-deleted thymic epithelian cells (TEC) have normal function. Our data suggest that heavy redundancy and promiscuous interaction between EPHs and EFNs compensate for the missing EPHB4 in TECs, and TEC EPHB4's role in T cell development might only be revealed if multiple EPHs are ablated simultaneously. We cannot exclude the possibility that (1) some immunological parameters not examined in this study are affected by the deletion; (2) the deletion is not complete due to the leaky Cre-LoxP system, and the remaining EPHB4 in TEC is sufficient for thymocyte development; or (3) EPHB4 expression in TEC is not required for T cell development and function.
Laboratoire d'immunologie and Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
Wei
W
Jin
Laboratoire d'immunologie and Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
Hongyu
H
Luo
Laboratoire d'immunologie and Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada; Service de néphrologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada. Electronic address: jianping.wu@umontreal.ca.
Jiangping
J
Wu
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D036342:Ephrins / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D036224:Receptor, EphB4 / Q000235:genetics / Q000502:physiology*; D036081:Receptors, Eph Family / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
D036342:Ephrins; D012333:RNA, Messenger; C086681:Ephb4 protein, mouse; D036224:Receptor, EphB4; D036081:Receptors, Eph Family
Eph; T cell development; T cell function; Thymic epithelial cell