title: A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide.
abstract: Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In the presence of LPS, RGMa siRNA transfection markedly reduced levels of CD80, CD86, CD40, and MHC II expression, as well as the secretion of IL-12p70 and TNF-α. With LPS treatment, RGMa siRNA-transfected DCs also showed increased levels of IL-10 and endocytosis. Moreover, in the presence of LPS, RGMa siRNA-transfected DCs displayed a low ability to induce T cell proliferation and differentiation, compared with negative control (NTi)-transfected or control DCs (p<0.05 for both). We conclude that after LPS stimulation, RGMa siRNA-transfected DCs show immunoregulatory and tolerogenic characteristics, which provides new insights into the immune system.
authors.affiliation: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors.forename: Xuxu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110000, PR China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Shan
authors.affiliation: Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, PR China. Electronic address: cmufengjuan@sina.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C483496:Rgma protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12
keywords: Dendritic cells; Immune regulation; Maturation; RGMa; Tolerance; siRNA