title: Anti-CD40 Ab- or 8-oxo-dG-enhanced Treg cells reduce development of experimental autoimmune encephalomyelitis via down-regulating migration and activation of mast cells.
abstract: This study investigated whether anti-CD40 Ab and 8-oxo-dG attenuate mast cell migration and EAE development. Anti-CD40 Ab and 8-oxo-dG reduced EAE scores, mast cell numbers, expression of adhesion molecules, OX40L and Act1, levels of TNF-α, LTs, expression of cytokines, and co-localization of Treg cells and mast cells, all of which are increased in EAE-brain tissues. Each treatment enhanced Treg cells, expression of OX40, and cytokines related to suppressive function of Treg cells in EAE brain tissues. Act-BMMCs with Treg cells reduced expression of OX40L and CCL2/CCR2, VCAM-1, PECAM-1, [Ca²⁺]i levels, release of mediators, various signaling molecules, Act1 related to IL-17a signals versus those in act-BMMCs without Treg cells. The data suggest that IL-10- and IL-35-producing Foxp3⁺-Treg cells, enhanced by anti-CD40 Ab or 8-oxo-dG, suppress migration of mast cells through down-regulating the expression of adhesion molecules, and suppress mast cell activation through cell-to-cell cross-talk via OX40/OX40L in EAE development.
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Gwan Ui
authors.initials: GU
authors.lastname: Hong
authors.forename: Nam Goo
authors.initials: NG
authors.lastname: Kim
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D019013:CD40 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D015289:Leukotrienes; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D002118:Calcium