title: Aberrant responses to TLR agonists in pediatric IBD patients; the possible association with increased production of Th1/Th17 cytokines in response to candida, a luminal antigen.
abstract: Toll like receptors (TLR) regulate innate immune responses sensing byproducts of intestinal microbiota. We examined responses to TLR agonists in children with inflammatory bowel disease (IBD). Peripheral blood mononuclear cells (PBMC) obtained from children with IBD [Crohn's disease (CD, n = 10), ulcerative colitis (UC, n = 10)], children with non-IgE-mediated food allergy (NFA, n = 20), and controls (n = 15) were tested for their production of proinflammatory and counter-regulatory cytokines with TLR agonists in comparison with their cytokine production against milk protein and candida. IBD patients were all in the inactive state. IBD PBMC produced more IL-6 with all the TLR agonists tested than controls. CD PBMC produced more counter-regulatory cytokines with TLR agonists, while UC PBMC produced more IL-1ss and IL-10 with TLR 7/8 agonist than controls. Cytokine production by NFA PBMC did not differ from controls. CD but not UC PBMC produced more IFN-gamma and IL-17 with candida. Aberrant responses to TLR agonists may be associated with increase in IFN-gamma/IL-17 production against candida in CD children.
authors.affiliation: Division of Allergy/Immunology and Infectious Diseases, University of Medicine and Dentistry of New Jersey (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ 07101-1709, USA. jyanouha@umdnj.edu
authors.forename: Harumi
authors.initials: H
authors.lastname: Jyonouchi
authors.forename: Lee
authors.initials: L
authors.lastname: Geng
authors.forename: Agnes
authors.initials: A
authors.lastname: Cushing-Ruby
authors.forename: Iona M
authors.initials: IM
authors.lastname: Monteiro
mesh_terms: D000293:Adolescent; D002175:Candida / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000382:microbiology; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors