title: In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses.
abstract: Alterations in the gut microbiota composition are associated with food allergy. Toll-like receptors (TLRs) respond to microbial stimuli. We studied the effects of the ligation of TLRs on intestinal epithelial cells (IECs) in preventing an allergic effector response. IEC monolayers (T84 cells) were co-cultured with CD3/28-activated PBMCs from healthy controls or atopic patients and simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier integrity of T84 cell monolayers was significantly reduced upon co-culture with PBMCs of food allergic subjects compared to healthy subjects. Apical exposure of IECs to a TLR9 ligand prevented PBMC-induced epithelial barrier disruption. Using PBMCs from food allergic subjects, apical TLR9 activation on IECs increased the IFN-γ/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6, IL-8 and TNF-α production in an IEC-dependent manner. Hence, the activation of apical TLR9 on IECs, potentially by microbiota-derived signals, may play an important role in the prevention of allergic inflammation.
authors: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA. Electronic address: sander_dekivit@rush.edu.
authors: Sander
authors: S
authors: de Kivit
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Mary C
authors: MC
authors: Tobin
authors: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA.
authors: Mark T
authors: MT
authors: DeMeo
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Susan
authors: S
authors: Fox
authors: Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands; Department of Immunology, Nutricia Research, The Netherlands.
authors: Johan
authors: J
authors: Garssen
authors: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA.
authors: Christopher B
authors: CB
authors: Forsyth
authors: Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors: Ali
authors: A
authors: Keshavarzian
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors: Alan L
authors: AL
authors: Landay
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051193:Toll-Like Receptors
keywords: Cytokines;; Food allergy;; Intestinal epithelial cells;; PBMC;; Toll-like receptors