title: Involvement of the iNKT cell pathway is associated with early-onset eosinophilic esophagitis and response to allergen avoidance therapy.
abstract: OBJECTIVE
  Recent experimental evidence suggests that environmental microbial factors early in life determine susceptibility to allergic diseases through inappropriate chemotaxis and local activation of CD1d-restricted, invariant chain natural killer T (iNKT) cells. In this study, we analyzed the involvement of these pathways in pediatric patients with eosinophilic esophagitis (EoE) before and after dietary allergen elimination.
  
  
  METHODS
  mRNA expression levels of components of the C-X-C motif chemokine ligand 16 (CXCL16)-iNKT-CD1d axis were compared in esophageal biopsies from EoE patients vs. normal or inflammatory controls and before and after treatment.
  
  
  RESULTS
  CXCL16, iNKT cell-associated cell marker Vα24, and CD1d were significantly upregulated in esophageal biopsies from EoE patients and correlated with the expression of inflammatory mediators associated with allergy. Upregulation of each of these factors was significantly more pronounced in patients aged <6 years at diagnosis, and this early-onset EoE subpopulation was characterized by a more prominent food allergic disease phenotype in a cohort-wide analysis. Successful, but not unsuccessful, treatment of early-onset EoE patients with dietary elimination of instigating allergens led to reduction in infiltrating iNKT cells and complete normalization of mRNA expression levels of CXCL16 and CD1d.
  
  
  CONCLUSIONS
  Our observations place iNKT cells at the center of allergic inflammation associated with EoE, which could have profound implications for our understanding, treatment and prevention of this and other human allergic diseases.
authors: Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Willem S
authors: WS
authors: Lexmond
authors: Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Joana F
authors: JF
authors: Neves
authors: Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Samuel
authors: S
authors: Nurko
authors: Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Torsten
authors: T
authors: Olszak
authors: Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Mark A
authors: MA
authors: Exley
authors: 1] Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA [2] These authors contributed equally to this work.
authors: Richard S
authors: RS
authors: Blumberg
authors: 1] Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA [2] These authors contributed equally to this work.
authors: Edda
authors: E
authors: Fiebiger
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D055610:Antigens, CD1d / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis; D002648:Child; D002675:Child, Preschool; D004035:Diet Therapy; D057765:Eosinophilic Esophagitis / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D004947:Esophagus / Q000276:immunology* / Q000473:pathology; D005260:Female; D005512:Food Hypersensitivity / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D055611:Natural Killer T-Cells / Q000378:metabolism*; D010641:Phenotype; D011446:Prospective Studies; D051116:Receptors, Scavenger / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D055610:Antigens, CD1d; D015415:Biomarkers; C526877:CD1D protein, human; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D051116:Receptors, Scavenger