IL-4 triggers autoimmune diabetes by increasing self-antigen presentation within the pancreatic islets

Marika Falcone, Brian Yeung, Lee Tucker, Enrique Rodriguez, Troy Krahl, Nora Sarvetnick

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Several findings have recently questioned the long held hypothesis that cytokines belonging to the Th2 pathway are protective in T-cell-mediated autoimmunity. Among them, there is our previous report that pancreatic expression of IL-4 activated islet antigen-specific BDC2.5 T cells and rendered them able to trigger insulin-dependent diabetes mellitus in ins-IL-4/BDC2.5 mice (Mueller et al., Immunity, 7, 1997). Here we analyze the mechanisms underlying IL-4-mediated activation of the self-reactive BDC2.5 T cells. IL-4 is mainly known as the Th2-driving cytokine. However, IL-4 is also critical for DC maturation and upregulation of antigen uptake and presentation by macrophages. In our model, we found that pancreatic expression of IL-4 activated self-reactive BDC2.5 T cells by increasing islet antigen presentation by macrophages and dendritic cells. IL-4 could have triggered self-antigen presentation within the pancreatic islets both by driving maturation of DC from a tolerizing to a priming state and by increasing self-antigen uptake by macrophages.

Original languageEnglish (US)
Pages (from-to)190-199
Number of pages10
JournalClinical Immunology
Volume98
Issue number2
DOIs
StatePublished - Jan 1 2001

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Autoantigens
Antigen Presentation
Type 1 Diabetes Mellitus
Islets of Langerhans
Interleukin-4
T-Lymphocytes
Macrophages
Cytokines
Autoimmunity
Dendritic Cells
Immunity
Up-Regulation
Antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-4 triggers autoimmune diabetes by increasing self-antigen presentation within the pancreatic islets. / Falcone, Marika; Yeung, Brian; Tucker, Lee; Rodriguez, Enrique; Krahl, Troy; Sarvetnick, Nora.

In: Clinical Immunology, Vol. 98, No. 2, 01.01.2001, p. 190-199.

Research output: Contribution to journalArticle

Falcone, Marika ; Yeung, Brian ; Tucker, Lee ; Rodriguez, Enrique ; Krahl, Troy ; Sarvetnick, Nora. / IL-4 triggers autoimmune diabetes by increasing self-antigen presentation within the pancreatic islets. In: Clinical Immunology. 2001 ; Vol. 98, No. 2. pp. 190-199.
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