title: Role of EFNB1 and EFNB2 in Mouse Collagen-Induced Arthritis and Human Rheumatoid Arthritis.
abstract: OBJECTIVE
  EFNB1 and EFNB2 are ligands for Eph receptor tyrosine kinases. This study was undertaken to investigate how the expression of Efnb1 and Efnb2 on murine T cells influences the pathogenesis of collagen-induced arthritis (CIA) and to assess correlations between the T cell expression of these 2 molecules and measures of disease activity in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  CIA was studied in mice with T cell-specific deletion (double gene knockout [dKO]) of both Efnb1 and Efnb2. Expression of EFNB1 and EFNB2 messenger RNA (mRNA) in peripheral blood T cells from patients with RA was determined by quantitative reverse transcription- polymerase chain reaction.
  
  
  RESULTS
  In dKO mice, clinical scores of arthritis were reduced compared to those in wild-type (WT) control mice. Serum collagen-specific antibody titers in dKO mice were lower than those in WT mice. In analyses based on equal cell numbers, dKO mouse T cells, as compared to WT mouse T cells, provided vastly inferior help to B cells in the production of collagen-specific antibodies in vitro. T cells from dKO mice were compromised in their ability to migrate to the arthritic paws in vivo and in their ability to undergo chemotaxis toward CXCL12 in vitro. Deletion mutation of Efnb1 and Efnb2 intracellular tails revealed critical regions in controlling T cell chemotaxis. T cells from RA patients expressed higher EFNB1 mRNA levels, which correlated with RA symptoms and laboratory findings.
  
  
  CONCLUSIONS
  Efnb1 and Efnb2 in T cells are essential for pathogenic antibody production and for T cell migration to the inflamed paws in mice with CIA. These findings suggest that the expression of EFNB1 in T cells might be a useful parameter for monitoring RA disease activity and treatment responses.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Wang
authors.affiliation: West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Cheng
authors.affiliation: First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Fang
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Junzheng
authors.initials: J
authors.lastname: Peng
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Shijie
authors.initials: S
authors.lastname: Qi
authors.affiliation: First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Guixiu
authors.initials: G
authors.lastname: Shi
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D004195:Disease Models, Animal; D036387:Ephrin-B1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D036388:Ephrin-B2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: C484288:EFNB1 protein, human; C000601239:EFNB2 protein, human; C000601240:EFNB2 protein, mouse; C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D036388:Ephrin-B2