UMass Chan Medical School Faculty Publications

UMMS Affiliation

Department of Medicine; Diabetes Center of Excellence; Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences

Publication Date

2021-10-26

Document Type

Article

Disciplines

Endocrine System Diseases | Endocrinology, Diabetes, and Metabolism | Immune System Diseases | Immunology and Infectious Disease | Nutritional and Metabolic Diseases

Abstract

Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing beta 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.

Keywords

diabetes, immunity, autoimmunity

Rights and Permissions

Copyright © 2021 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license.

DOI of Published Version

10.4049/immunohorizons.2100088

Source

Qaisar N, Arowosegbe A, Derr AG, Kucukural A, Satish B, Racicot R, Guo Z, Trombly MI, Wang JP. Type I IFN-Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes. Immunohorizons. 2021 Oct 26;5(10):855-869. doi: 10.4049/immunohorizons.2100088. PMID: 34702762. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

ImmunoHorizons

PubMed ID

34702762

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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