title: Elevated expression of CX3C chemokine receptor 1 mediates recruitment of T cells into bone marrow of patients with acquired aplastic anaemia.
abstract: OBJECTIVE
  Acquired aplastic anaemia (AA) is a T-cell-mediated, organ-specific autoimmune disease characterized by haematopoietic stem cell destruction in the bone marrow. The exact molecular mechanism of T-cell trafficking into the bone marrow is unclear in AA. Very late activation antigen-4 (VLA-4) and CX3C chemokine receptor 1 (CX3CR1) play active roles in many autoimmune diseases. Therefore, we investigated whether VLA-4 and CX3CR1 also contribute to T-cell migration into the bone marrow in acquired AA.
  
  
  METHODS
  Expression levels of CX3CR1 and VLA-4 and their ligands [fractalkine (CX3CL1) and vascular cell adhesion molecule-1 (VCAM-1)] were examined in 63 patients with AA and 21 healthy control subjects. T-cell chemotaxis and adhesion were analysed in 17 patients with severe AA. We also prospectively evaluated the expression pattern of CX3CR1 during treatment with antithymocyte globulin plus cyclosporine in 11 patients with severe AA.
  
  
  RESULTS
  The proportion of peripheral and bone marrow CD4(+) and CD8(+) T cells expressing CX3CR1 and the level of CX3CL1 was increased in patients with AA. However, there was no significant difference in VLA-4 expression or VCAM-1 levels. Functional studies demonstrated that chemotaxis towards autologous bone marrow plasma or soluble CX3CL1 was significantly higher in T cells from AA patients and could be blocked by CX3CR1 inhibitors. CX3CR1-mediated T-cell adhesion was also upregulated in these patients. The expression of CX3CR1 was associated with the efficacy of immunosuppressive therapy.
  
  
  CONCLUSIONS
  The present findings demonstrate that CX3CR1 plays a pivotal role in recruitment of T cells into the bone marrow in acquired AA and is a potential therapeutic target for treatment of this disorder.
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Department of Hematology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
authors: J
authors: J
authors: Ren
authors: X Y
authors: XY
authors: Hou
authors: S H
authors: SH
authors: Ma
authors: F K
authors: FK
authors: Zhang
authors: J H
authors: JH
authors: Zhen
authors: L
authors: L
authors: Sun
authors: Y X
authors: YX
authors: Sun
authors: Y L
authors: YL
authors: Hao
authors: Y F
authors: YF
authors: Cheng
authors: M
authors: M
authors: Hou
authors: C G
authors: CG
authors: Xu
authors: M H
authors: MH
authors: Zhang
authors: J
authors: J
authors: Peng
mesh_terms: D000741:Anemia, Aplastic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D016572:Cyclosporine / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D039041:Integrin alpha4beta1 / Q000097:blood / Q000378:metabolism*; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000097:blood / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism
chemical_list: D000961:Antilymphocyte Serum; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D016572:Cyclosporine
keywords: CX3C chemokine receptor 1; T cells; aplastic anaemia; very late activation antigen-4