Interferon alpha

The key trigger of type 1 diabetes

Angela Lombardi, Effie Tsomos, Sara S. Hammerstad, Yaron Tomer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

IFNα is a cytokine essential to a vast array of immunologic processes. Its induction early in the innate immune response provides a priming mechanism that orchestrates numerous subsequent pathways in innate and adaptive immunity. Despite its beneficial effects in viral infections IFNα has been reported to be associated with several autoimmune diseases including autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary cholangitis, and recently emerged as a major cytokine that triggers Type 1 Diabetes. In this review, we dissect the role of IFNα in T1D, focusing on the potential pathophysiological mechanisms involved. Evidence from human and mouse studies indicates that IFNα plays a key role in enhancing islet expression of HLA-I in patients with T1D, thereby increasing autoantigen presentation and beta cell activation of autoreactive cytotoxic CD8 T-lymphocytes. The binding of IFNα to its receptor induces the secretion of chemokines, attracting monocytes, T lymphocytes, and NK cells to the infected tissue triggering autoimmunity in susceptible individuals. Furthermore, IFNα impairs insulin production through the induction of endoplasmic reticulum stress as well as by impairing mitochondrial function. Due to its central role in the early phases of beta cell death, targeting IFNα and its pathways in genetically predisposed individuals may represent a potential novel therapeutic strategy in the very early stages of T1D.

Original languageEnglish (US)
JournalJournal of Autoimmunity
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Type 1 Diabetes Mellitus
Innate Immunity
Interferon-alpha
Autoimmune Diseases
Cytokines
Endoplasmic Reticulum Stress
Cholangitis
Thyroid Diseases
Autoantigens
Cytotoxic T-Lymphocytes
Adaptive Immunity
Virus Diseases
Autoimmunity
Chemokines
Natural Killer Cells
Systemic Lupus Erythematosus
Monocytes
Rheumatoid Arthritis
Cell Death
Insulin

Keywords

  • Interferon alpha
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Interferon alpha : The key trigger of type 1 diabetes. / Lombardi, Angela; Tsomos, Effie; Hammerstad, Sara S.; Tomer, Yaron.

In: Journal of Autoimmunity, 01.01.2018.

Research output: Contribution to journalArticle

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