Type-I interferons inhibit interleukin-10 signaling and favor Type 1 diabetes development in nonobese diabetic mice

Marcos Iglesias, Anirudh Arun, Maria Chicco, Brandon Lam, C. Conover Talbot, Vera Ivanova, W. P.A. Lee, Gerald Brandacher, Giorgio Raimondi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Destruction of insulin-producing β-cells by autoreactive T lymphocytes leads to the development of type 1 diabetes. Type-I interferons (TI-IFN) and interleukin-10 (IL-10) have been connected with the pathophysiology of this disease; however, their interplay in the modulation of diabetogenic T cells remains unknown. We have discovered that TI-IFN cause a selective inhibition of IL-10 signaling in effector and regulatory T cells, altering their responses. This correlates with diabetes development in nonobese diabetic mice, where the inhibition is also spatially localized to T cells of pancreatic and mesenteric lymph nodes. IL-10 signaling inhibition is reversible and can be restored via blockade of TI-IFN/IFN-R interaction, paralleling with the resulting delay in diabetes onset and reduced severity. Overall, we propose a novel molecular link between TI-IFN and IL-10 signaling that helps better understand the complex dynamics of autoimmune diabetes development and reveals new strategies of intervention.

Original languageEnglish (US)
Article number1565
JournalFrontiers in immunology
Volume9
Issue numberJUL
DOIs
StatePublished - Jul 16 2018
Externally publishedYes

Fingerprint

Interferon Type I
Inbred NOD Mouse
Type 1 Diabetes Mellitus
Interleukin-10
T-Lymphocytes
Regulatory T-Lymphocytes
Lymph Nodes
Insulin

Keywords

  • Interleukin-10 signaling
  • Nonobese diabetic mice
  • T lymphocytes
  • Type 1 diabetes
  • Type-I interferons

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Type-I interferons inhibit interleukin-10 signaling and favor Type 1 diabetes development in nonobese diabetic mice. / Iglesias, Marcos; Arun, Anirudh; Chicco, Maria; Lam, Brandon; Talbot, C. Conover; Ivanova, Vera; Lee, W. P.A.; Brandacher, Gerald; Raimondi, Giorgio.

In: Frontiers in immunology, Vol. 9, No. JUL, 1565, 16.07.2018.

Research output: Contribution to journalArticle

Iglesias, M, Arun, A, Chicco, M, Lam, B, Talbot, CC, Ivanova, V, Lee, WPA, Brandacher, G & Raimondi, G 2018, 'Type-I interferons inhibit interleukin-10 signaling and favor Type 1 diabetes development in nonobese diabetic mice', Frontiers in immunology, vol. 9, no. JUL, 1565. https://doi.org/10.3389/fimmu.2018.01565
Iglesias, Marcos ; Arun, Anirudh ; Chicco, Maria ; Lam, Brandon ; Talbot, C. Conover ; Ivanova, Vera ; Lee, W. P.A. ; Brandacher, Gerald ; Raimondi, Giorgio. / Type-I interferons inhibit interleukin-10 signaling and favor Type 1 diabetes development in nonobese diabetic mice. In: Frontiers in immunology. 2018 ; Vol. 9, No. JUL.
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