title: Thymic-derived tolerizing dendritic cells are upregulated in the spleen upon treatment with intravenous immunoglobulin in a murine model of immune thrombocytopenia.
abstract: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by low platelet counts. First-line treatment includes intravenous immunoglobulin (IVIg), however, its working mechanism remains incompletely understood. We investigated splenic and thymic dendritic cell (DC) subsets upon IVIg treatment in a well-characterized active murine model of ITP. During active disease, there was a significant peripheral deficiency of splenic tolerizing SIRPα+ DCs which could be rescued by IVIg therapy, increasing platelet counts. These splenic tolerizing DC changes were associated with an abrogation of the thymic-retention of tolerizing DCs, suggesting that IVIg may raise platelet counts in ITP by modulating peripheral numbers of tolerizing DCs.
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.|b Canadian Blood Services , Toronto , ON , Canada.
authors.forename: Rick
authors.initials: R
authors.lastname: Kapur
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Aslam
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.|b Canadian Blood Services , Toronto , ON , Canada.|c Department of Medicine , University of Toronto , Toronto , ON , Canada.|d Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , ON , Canada.
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.affiliation: e Department of Medicine , University of Rochester School of Medicine , Rochester , NY , USA.
authors.forename: George B
authors.initials: GB
authors.lastname: Segel
authors.affiliation: a The Toronto Platelet Immunobiology Group , Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto , ON , Canada.|b Canadian Blood Services , Toronto , ON , Canada.|c Department of Medicine , University of Toronto , Toronto , ON , Canada.|d Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , ON , Canada.|f Department of Pharmacology , University of Toronto , Toronto , ON , Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000187:drug effects*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Dendritic cells; IVIg; immune thrombocytopenia