Cargando…
Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes
Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing β cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)–mediated signaling pathways, likely contrib...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109816/ https://www.ncbi.nlm.nih.gov/pubmed/34702762 http://dx.doi.org/10.4049/immunohorizons.2100088 |
_version_ | 1784708962437824512 |
---|---|
author | Qaisar, Natasha Arowosegbe, Adediwura Derr, Alan G. Kucukural, Alper Satish, Basanthi Racicot, Riccardo Guo, Zhiru Trombly, Melanie I. Wang, Jennifer P. |
author_facet | Qaisar, Natasha Arowosegbe, Adediwura Derr, Alan G. Kucukural, Alper Satish, Basanthi Racicot, Riccardo Guo, Zhiru Trombly, Melanie I. Wang, Jennifer P. |
author_sort | Qaisar, Natasha |
collection | PubMed |
description | Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing β cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)–mediated signaling pathways, likely contribute to human type 1 diabetes susceptibility. We previously showed that LEW.1WR1 Ifnar1(−/−) rats have a significant reduction in diabetes frequency following Kilham rat virus (KRV) infection. To delineate the impact of IFNAR loss on immune cell populations in KRV-induced diabetes, we performed flow cytometric analysis in spleens from LEW.1WR1 wild-type (WT) and Ifnar1(−/−) rats after viral infection but before the onset of insulitis and diabetes. We found a relative decrease in CD8(+) T cells and NK cells in KRV-infected LEW.1WR1 Ifnar1(−/−) rats compared with KRV-infected WT rats; splenic regulatory T cells were diminished in WT but not Ifnar1(−/−) rats. In contrast, splenic neutrophils were increased in KRV-infected Ifnar1(−/−) rats compared with KRV-infected WT rats. Transcriptional analysis of splenic cells from KRV-infected rats confirmed a reduction in IFN-stimulated genes in Ifnar1(−/−) compared with WT rats and revealed an increase in transcripts related to neutrophil chemotaxis and MHC class II. Single-cell RNA sequencing confirmed that MHC class II transcripts are increased in monocytes and macrophages and that numerous types of splenic cells harbor KRV. Collectively, these findings identify dynamic shifts in innate and adaptive immune cells following IFNAR disruption in a rat model of autoimmune diabetes, providing insights toward the role of type I IFNs in autoimmunity. |
format | Online Article Text |
id | pubmed-9109816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-91098162022-05-16 Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes Qaisar, Natasha Arowosegbe, Adediwura Derr, Alan G. Kucukural, Alper Satish, Basanthi Racicot, Riccardo Guo, Zhiru Trombly, Melanie I. Wang, Jennifer P. Immunohorizons Article Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing β cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)–mediated signaling pathways, likely contribute to human type 1 diabetes susceptibility. We previously showed that LEW.1WR1 Ifnar1(−/−) rats have a significant reduction in diabetes frequency following Kilham rat virus (KRV) infection. To delineate the impact of IFNAR loss on immune cell populations in KRV-induced diabetes, we performed flow cytometric analysis in spleens from LEW.1WR1 wild-type (WT) and Ifnar1(−/−) rats after viral infection but before the onset of insulitis and diabetes. We found a relative decrease in CD8(+) T cells and NK cells in KRV-infected LEW.1WR1 Ifnar1(−/−) rats compared with KRV-infected WT rats; splenic regulatory T cells were diminished in WT but not Ifnar1(−/−) rats. In contrast, splenic neutrophils were increased in KRV-infected Ifnar1(−/−) rats compared with KRV-infected WT rats. Transcriptional analysis of splenic cells from KRV-infected rats confirmed a reduction in IFN-stimulated genes in Ifnar1(−/−) compared with WT rats and revealed an increase in transcripts related to neutrophil chemotaxis and MHC class II. Single-cell RNA sequencing confirmed that MHC class II transcripts are increased in monocytes and macrophages and that numerous types of splenic cells harbor KRV. Collectively, these findings identify dynamic shifts in innate and adaptive immune cells following IFNAR disruption in a rat model of autoimmune diabetes, providing insights toward the role of type I IFNs in autoimmunity. 2021-10-26 /pmc/articles/PMC9109816/ /pubmed/34702762 http://dx.doi.org/10.4049/immunohorizons.2100088 Text en https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the CC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Qaisar, Natasha Arowosegbe, Adediwura Derr, Alan G. Kucukural, Alper Satish, Basanthi Racicot, Riccardo Guo, Zhiru Trombly, Melanie I. Wang, Jennifer P. Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title | Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title_full | Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title_fullStr | Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title_full_unstemmed | Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title_short | Type I IFN–Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes |
title_sort | type i ifn–driven immune cell dysregulation in rat autoimmune diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109816/ https://www.ncbi.nlm.nih.gov/pubmed/34702762 http://dx.doi.org/10.4049/immunohorizons.2100088 |
work_keys_str_mv | AT qaisarnatasha typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT arowosegbeadediwura typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT derralang typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT kucukuralalper typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT satishbasanthi typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT racicotriccardo typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT guozhiru typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT tromblymelaniei typeiifndrivenimmunecelldysregulationinratautoimmunediabetes AT wangjenniferp typeiifndrivenimmunecelldysregulationinratautoimmunediabetes |