Decreased dendritic cell numbers but increased TLR9-mediated interferon-alpha production in first degree relatives of type 1 diabetes patients

Clin Immunol. 2014 Jul;153(1):49-55. doi: 10.1016/j.clim.2014.03.018. Epub 2014 Apr 5.

Abstract

Objective: Dendritic cells (DCs) play an important role in pathogenesis of autoimmunity, including type 1 diabetes (T1D). In this study, we investigated DC subpopulations and their responses to TLR stimulation in T1D patients and their relatives.

Methods: We analyzed the frequency of myeloid (mDCs) and plasmacytoid DCs (pDCs) in 97 T1D patients (69 onset, 28 long-term), 67 first-degree relatives, and 64 controls. We additionally tested the IFN-alpha production by pDCs upon stimulation with TLR 7, 8 and 9 agonists.

Results: A lower number of mDCs and pDCs were found in T1D patients and their relatives. Of all the tested TLR ligands, only stimulation with CpG 2216 induced IFN-alpha production that was the highest in T1D relatives, except of autoantibody-negative relatives bearing the protective haplotypes.

Conclusion: Our data demonstrate disturbances in DC number and function expressed most significantly in T1D relatives and point to a potential role of TLR9-induced IFN-alpha production in T1D development.

Keywords: Dendritic cell;; Interferon-alpha;; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Count
  • Child
  • Child, Preschool
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Family
  • Female
  • Humans
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / blood
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Ligands
  • Male
  • Oligodeoxyribonucleotides / pharmacology
  • Toll-Like Receptor 9 / metabolism*
  • Young Adult

Substances

  • CpG ODN 2216
  • Interferon-alpha
  • Ligands
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9