title: Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.
abstract: The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D) pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs) from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Thornley
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Krishna A
authors.initials: KA
authors.lastname: Agarwal
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Periklis
authors.initials: P
authors.lastname: Kyriazis
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Vaja
authors.initials: V
authors.lastname: Chipashvili
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Aker
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Sarantis
authors.initials: S
authors.lastname: Korniotis
authors.affiliation: Department of Surgery, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Csizmadia
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.|Department of Surgery, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.affiliation: Department of Medicine, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.|Department of Surgery, Harvard Medical School and the Transplant Institute at Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Koulmanda
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology*; D008264:Macrophages / Q000276:immunology*; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D051197:Toll-Like Receptor 4