Monocytes Differentiated with IL-15 Support Th17 and Th1 Responses to Wheat Gliadin: Implications for Celiac Disease

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2010 Feb 16

PMID 20153259

Citations 33

Authors

Kristina M Harris

Alessio Fasano

Dean L Mann

Affiliations

Soon will be listed here.

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.

Citing Articles

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Immunomodulatory and Anti-Inflammatory Effects of Vitamin A and Tryptophan on Monocyte-Derived Dendritic Cells Stimulated with Gliadin in Celiac Disease Patients.

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Akkermansia muciniphila exerts immunomodulatory and anti-inflammatory effects on gliadin-stimulated THP-1 derived macrophages.

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