title: Invariant natural killer T-cell neutralization is a possible novel therapy for human eosinophilic esophagitis.
abstract: Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disorder that needs a potential therapeutic strategy. We earlier showed that iNKT cell-deficient mice are protected from allergen-induced EoE. Therefore, we now tested the hypothesis that iNKT cells are induced in the human EoE and is a novel possible target for the treatment of human EoE. Accordingly, we examine number of iNKT cells and eosinophils and expression of iNKT-associated cell surface receptors and chemokines by performing immunofluorescence, qPCR and ELISA in the esophageal biopsies and blood samples of normal subjects (comparison control) and EoE patients. Herein, we show that iNKT cell number, their receptor subcomponents Vα24 and Vβ11 expression, and associated chemokine CXCL16 levels (or expression) are induced significantly in EoE patients compared with normal individuals. In addition, we show that CXCL16 levels (or expression) correlate with the mRNA levels of Vα24 receptor but not well with esophageal eosinophilia in human EoE. Of note, we show that in vivo activation of iNKT cells is sufficient to induce EoE in mice. Furthermore, we show that anti-mCD1d- and anti-hVα24Jα18-neutralizing antibody treatment protects allergen-induced experimental EoE. Taken together, we have shown first time that iNKT cells have a critical pathogenic role in human and experimental EoE. iNKT cell neutralization by humanized anti-CD1d and anti-Vα24Jα18 antibodies might be a novel and potential therapy for human EoE.
authors.affiliation: Department of Pathology, University of Cincinnati , Cincinnati, OH, USA.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rayapudi
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH , USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Rajavelu
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center , Cincinnati, OH, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Division of Gastroenterology and Liver Disease, Case Western Reserve University , Cleveland, OH, USA.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Niranjan
authors.affiliation: Division of Gastroenterology and Liver Disease, Case Western Reserve University , Cleveland, OH, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Dynda
authors.affiliation: Biomedical Engineering, Case Western Reserve University , Cleveland, OH, USA.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center ; Cincinnati, OH, USA ; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 , Erlangen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Mattner
authors.affiliation: Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA.
authors.forename: Asifa
authors.initials: A
authors.lastname: Zaidi
authors.affiliation: Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA.
authors.forename: Parmesh
authors.initials: P
authors.lastname: Dutt
authors.affiliation: Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
keywords: CXCL16; PBS57; anti-CD1d; anti-Vα24Jα18; iNKT cells