Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes

• Published in: PloS one Vol. 11; no. 3; p. e0150792
• Main Authors: Thornley, Thomas B, Agarwal, Krishna A, Kyriazis, Periklis, Ma, Lingzhi, Chipashvili, Vaja, Aker, Jonathan E, Korniotis, Sarantis, Csizmadia, Eva, Strom, Terry B, Koulmanda, Maria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.03.2016; Public Library of Science (PLoS)
• Subjects: Abundance; Adaptive immunity; Adaptive systems; Animals; Antigens; Antigens, CD - metabolism; Biology and Life Sciences; Comparative analysis; Cytokines; Dendritic cells; Dendritic Cells - immunology; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Female; Forkhead Transcription Factors - metabolism; Foxp3 protein; Genetic aspects; Genomes; Genotype & phenotype; Glucose; Immune response; Immune system; Immunity; Immunology; Immunoregulation; Immunostimulation; Inflammation; Innate immunity; Islets of Langerhans - pathology; Laboratory animals; Macrophages; Macrophages - immunology; Medical schools; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Monocytes; Pathogenesis; Phenotype; Physiological aspects; Real-Time Polymerase Chain Reaction; Relative abundance; Rodents; Surgery; T-Lymphocytes, Regulatory - immunology; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transgenic animals; Type 1 diabetes; United States; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150792

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.