title: Efnb1 and Efnb2 proteins regulate thymocyte development, peripheral T cell differentiation, and antiviral immune responses and are essential for interleukin-6 (IL-6) signaling.
abstract: Erythropoietin-producing hepatocellular kinases (Eph kinases) constitute the largest family of cell membrane receptor tyrosine kinases, and their ligand ephrins are also cell surface molecules. Because of promiscuous interaction between Ephs and ephrins, there is considerable redundancy in this system, reflecting the essential roles of these molecules in the biological system through evolution. In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion. Mice with this double conditional mutation (double KO mice) showed reduced thymus and spleen size and cellularity. There was a significant decrease in the DN4, double positive, and single positive thymocyte subpopulations and mature CD4 and CD8 cells in the periphery. dKO thymocytes and peripheral T cells failed to compete with their WT counterparts in irradiated recipients, and the T cells showed compromised ability of homeostatic expansion. dKO naive T cells were inferior in differentiating into Th1 and Th17 effectors in vitro. The dKO mice showed diminished immune response against LCMV infection. Mechanistic studies revealed that IL-6 signaling in dKO T cells was compromised, in terms of abated induction of STAT3 phosphorylation upon IL-6 stimulation. This defect likely contributed to the observed in vitro and in vivo phenotype in dKO mice. This study revealed novel roles of Efnb1 and Efnb2 in T cell development and function.
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors: Hongyu
authors: H
authors: Luo
authors: Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Québec H7V 1B7, Canada.
authors: Tania
authors: T
authors: Charpentier
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors: Xuehai
authors: X
authors: Wang
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors: Shijie
authors: S
authors: Qi
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors: Bing
authors: B
authors: Han
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada; Institute of Cardiology, First Affiliated Hospital, Medical College, Zhejiang University, 310003 Hangzhou, China.
authors: Tao
authors: T
authors: Wu
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors: Rafik
authors: R
authors: Terra
authors: Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Québec H7V 1B7, Canada.
authors: Alain
authors: A
authors: Lamarre
authors: Laboratoire Immunologie, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada; Service Nephrologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada. Electronic address: jianping.wu@umontreal.ca.
authors: Jiangping
authors: J
authors: Wu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D036387:Ephrin-B1 / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D060168:Thymocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse