Eosinophils from patients with type 1 diabetes mellitus express high level of myeloid alpha-defensins and myeloperoxidase

Cell Immunol. 2012;273(2):158-63. doi: 10.1016/j.cellimm.2011.12.001. Epub 2012 Jan 2.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Recently, small cationic α-defensin molecules have been implicated in the pathogenesis of certain inflammatory and autoimmune diseases. The purpose of this study was to assess the α-defensin expression in patients with T1D and elucidate the cellular source of their production. Our results show that 30% of patients exhibit increased levels of α-defensin mRNAs in their capillary blood. Quantitative RT-PCR performed on FACS-sorted granulocytes identified CD15(dull)/CD14(weak) population as the cellular source of α-defensins. Surprisingly, this granulocyte subpopulation displayed augmentation of α-defensin expression in all T1D patients tested. The determination of cell surface markers, expression of cell-specific genes and confocal microscopy identified CD15(dull)/CD14(weak) cells as eosinophils. The presence of transcriptionally active eosinophils in diabetic patients suggests that eosinophils could be a part of an intricate innate immune cellular network involved in the development of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoimmunity
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immune Tolerance
  • Immunity, Innate
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Lewis X Antigen / immunology
  • Lipopolysaccharide Receptors / immunology
  • Peroxidase / blood
  • Peroxidase / genetics
  • Peroxidase / immunology*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • alpha-Defensins / blood
  • alpha-Defensins / genetics
  • alpha-Defensins / immunology*

Substances

  • Lewis X Antigen
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • alpha-Defensins
  • Peroxidase