Thymic stromal lymphopoietin–elicited basophil responses promote eosinophilic esophagitis

Item Type:	Article
Title:	Thymic stromal lymphopoietin–elicited basophil responses promote eosinophilic esophagitis
Creators Name:	Noti, M. and Wojno, E.D.T. and Kim, B.S. and Siracusa, M.C. and Giacomin, P.R. and Nair, M.G. and Benitez, A.J. and Ruymann, K.R. and Muir, A.B. and Hill, D.A. and Chikwava, K.R. and Moghaddam, A.E. and Sattentau, Q.J. and Alex, A. and Zhou, C. and Yearley, J.H. and Menard-Katcher, P. and Kubo, M. and Obata-Ninomiya, K. and Karasuyama, H. and Comeau, M.R. and Brown-Whitehorn, T. and de Waal Malefyt, R. and Sleiman, P.M. and Hakonarson, H. and Cianferoni, A. and Falk, G.W. and Wang, M.L. and Spergel, J.M. and Artis, D.
Abstract:	Eosinophilic esophagitis (EoE) is a food allergy–associated inflammatory disease characterized by esophageal eosinophilia. Current management strategies for EoE are nonspecific, and thus there is a need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis has been unclear. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE, but was dependent on TSLP and basophils, as targeting TSLP or basophils during the sensitization phase limited disease. Notably, therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. In human subjects with EoE, we observed elevated TSLP expression and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses in patients with EoE. Together, these data suggest that the TSLP-basophil axis contributes to the pathogenesis of EoE and could be therapeutically targeted to treat this disease.
Keywords:	Animal Disease Models, Basophils, Cytokines, Eosinophilic Esophagitis, Eosinophils, Esophagus, Immunoglobulin E, Inbred BALB C Mice, Inbred C57BL Mice, Monoclonal Antibodies, Neutralization Tests, Thymic Stromal Lymphopoietin, Animals, Mice
Source:	Nature Medicine
ISSN:	1546-170X
Publisher:	Nature Publishing Group
Volume:	19
Number:	8
Page Range:	1005-1013
Date:	August 2013
Official Publication:	https://doi.org/10.1038/nm.3281
PubMed:	View item in PubMed

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