Document Detail


Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: implications for celiac disease.
MedLine Citation:
PMID:  20153259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kristina M Harris; Alessio Fasano; Dean L Mann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-11
Journal Detail:
Title:  Clinical immunology (Orlando, Fla.)     Volume:  135     ISSN:  1521-7035     ISO Abbreviation:  Clin. Immunol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-11     Completed Date:  2010-06-09     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  100883537     Medline TA:  Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  430-9     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Affiliation:
Pathology Department, University of Maryland School of Medicine, Baltimore, MD, USA. kholt003@umaryland.edu
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MeSH Terms
Descriptor/Qualifier:
Celiac Disease / immunology*,  metabolism
Cell Differentiation / immunology*
Cell Separation
Cells, Cultured
Dendritic Cells / immunology,  metabolism
Flow Cytometry
Gene Expression Regulation / immunology*
Gliadin / immunology*
Humans
Interleukin-15 / biosynthesis,  genetics,  physiology*
Interleukin-17 / biosynthesis*
Lymphocyte Activation / immunology
Monocytes / cytology,  immunology*
Th1 Cells / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
DK078699/DK/NIDDK NIH HHS; R21 DK078699-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-15; 0/Interleukin-17; 9007-90-3/Gliadin
Comments/Corrections

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