An essential role of invariant natural killer T cells in the pathogenesis of eosinophilic esophagitis (59.1)

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (1_Supplement), p.59-59.1
• Main Authors: Mishra, Anil, Rajavelu, Priya, Rayapudi, Madhavi, Zhu, Xiang
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.59.1

Experimental eosinophilic esophagitis (EE) is a recently described chronic allergic inflammatory disorder whose basic pathogenesis is not well understood. Herein, we focus on the hypothesis that iNKT cell responses are essential for the initiation and progression of EE. We show that iNKT cells and their specific chemokine CXCL16 are induced in human and experimental EE. CXCL16 is primarily derived from esophageal epithelial cells and correlates with the levels of esophageal eosinophils. Notably, iNKT cell-deficient CD1d-null mice are protected from the induction of experimental EE; whereas, NK cell depleted mice exhibit full disease following allergen challenge. Interestingly, in vivo activation of human iNKT cells by the α-galactosylceramide analog PBS57 is sufficient to induce esophageal eosinophilia. Mechanistically, PBS57 exposed human iNKT cells produce IL-5 and IL-13 via STAT5 activation. Taken together, these findings provide evidence that iNKT cells have an essential pathogenic role in the initiation and progression of human and experimental EE, providing new opportunities for therapeutic strategies.