Monocytes Differentiated with IL-15 Support Th17 and Th1 Responses to Wheat Gliadin
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The research team included K. M. Harris, A. Fasano, and D. L. Mann of the Pathology Department at the University of Maryland School of Medicine.
It is understood that interleukin (IL)-15 contributes to the immuno-pathogenesis of celiac disease. However, the effect of IL-15 on APC that shape adaptive immune responses to gliadin is not well understood. Using PBMC from healthy individuals, the team demonstrated 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.
Compared with control subjects, PBMC from celiac disease patients showed lower concentrations of IL-15 augmented IFNgamma responses to PTG. So, by generating IL15-DC, IL-15 supports Th17 and Th1 responses to a dietary antigen that produces no such responses in healthy individuals. The team notes that IL-15 hypersensitivity may cause these potentially pathogenic immune responses to develop in celiac patients, but not in healthy individuals.
They conclude that the pathogenesis of celiac disease is likely due in part to genetic and/or environmental factors that control IL-15 expression and responsiveness in the gut.
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