Cargando…
Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes
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 tha...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778921/ https://www.ncbi.nlm.nih.gov/pubmed/26943809 http://dx.doi.org/10.1371/journal.pone.0150792 |
_version_ | 1782419554550415360 |
---|---|
author | Thornley, Thomas B. Agarwal, Krishna A. Kyriazis, Periklis Ma, Lingzhi Chipashvili, Vaja Aker, Jonathan E. Korniotis, Sarantis Csizmadia, Eva Strom, Terry B. Koulmanda, Maria |
author_facet | Thornley, Thomas B. Agarwal, Krishna A. Kyriazis, Periklis Ma, Lingzhi Chipashvili, Vaja Aker, Jonathan E. Korniotis, Sarantis Csizmadia, Eva Strom, Terry B. Koulmanda, Maria |
author_sort | Thornley, Thomas B. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4778921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47789212016-03-23 Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes Thornley, Thomas B. Agarwal, Krishna A. Kyriazis, Periklis Ma, Lingzhi Chipashvili, Vaja Aker, Jonathan E. Korniotis, Sarantis Csizmadia, Eva Strom, Terry B. Koulmanda, Maria PLoS One Research Article 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. Public Library of Science 2016-03-04 /pmc/articles/PMC4778921/ /pubmed/26943809 http://dx.doi.org/10.1371/journal.pone.0150792 Text en © 2016 Thornley et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Thornley, Thomas B. Agarwal, Krishna A. Kyriazis, Periklis Ma, Lingzhi Chipashvili, Vaja Aker, Jonathan E. Korniotis, Sarantis Csizmadia, Eva Strom, Terry B. Koulmanda, Maria Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title | Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title_full | Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title_fullStr | Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title_full_unstemmed | Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title_short | Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes |
title_sort | contrasting roles of islet resident immunoregulatory macrophages and dendritic cells in experimental autoimmune type 1 diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778921/ https://www.ncbi.nlm.nih.gov/pubmed/26943809 http://dx.doi.org/10.1371/journal.pone.0150792 |
work_keys_str_mv | AT thornleythomasb contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT agarwalkrishnaa contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT kyriazisperiklis contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT malingzhi contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT chipashvilivaja contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT akerjonathane contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT korniotissarantis contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT csizmadiaeva contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT stromterryb contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes AT koulmandamaria contrastingrolesofisletresidentimmunoregulatorymacrophagesanddendriticcellsinexperimentalautoimmunetype1diabetes |