Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: implications for celiac disease

Clin Immunol. 2010 Jun;135(3):430-9. doi: 10.1016/j.clim.2010.01.003. Epub 2010 Feb 11.

Abstract

Interleukin (IL)-15 contributes to the immunopathogenesis of Celiac disease (CD). However, it is not clear how IL-15 affects APC that shape adaptive immune responses to the dietary antigen, gliadin. Using PBMC from healthy individuals, we show that monocytes differentiated with IL-15 (IL15-DC) produced IL-1beta, IL-6, IL-15, IL-23, TNFalpha and CCL20 in response to pepsin-trypsin digested gliadin (PTG) and activated contact-dependent Th17 and Th1 responses from autologous CD4(+) T cells. Lower concentrations of IL-15 augmented IFNgamma responses to PTG in PBMC from CD patients compared to controls. Thus, IL-15 supports Th17 and Th1 responses to a dietary antigen that is normally well-tolerated in healthy individuals by generating IL15-DC. These potentially pathogenic immune responses may result in CD patients and not healthy individuals as a consequence of IL-15 hypersensitivity. Therefore, genetic and/or environmental factors that control IL-15 expression and responsiveness in the intestine likely participate in the pathogenesis of CD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Celiac Disease / immunology*
  • Celiac Disease / metabolism
  • Cell Differentiation / immunology*
  • Cell Separation
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Gliadin / immunology*
  • Humans
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / genetics
  • Interleukin-15 / physiology*
  • Interleukin-17 / biosynthesis*
  • Lymphocyte Activation / immunology
  • Monocytes / cytology
  • Monocytes / immunology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism

Substances

  • Interleukin-15
  • Interleukin-17
  • Gliadin