Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: implications for celiac disease.
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.
Harris
Kristina M
KM
Pathology Department, University of Maryland School of Medicine, Baltimore, MD, USA. kholt003@umaryland.edu
Fasano
Alessio
A
Mann
Dean L
DL
D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D019409:Interleukin-15; D020381:Interleukin-17; D005903:Gliadin