title: Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
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.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Noti
authors.forename: Elia D Tait
authors.initials: ED
authors.lastname: Wojno
authors.forename: Brian S
authors.initials: BS
authors.lastname: Kim
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.forename: Paul R
authors.initials: PR
authors.lastname: Giacomin
authors.forename: Meera G
authors.initials: MG
authors.lastname: Nair
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Benitez
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Ruymann
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Muir
authors.forename: David A
authors.initials: DA
authors.lastname: Hill
authors.forename: Kudakwashe R
authors.initials: KR
authors.lastname: Chikwava
authors.forename: Amin E
authors.initials: AE
authors.lastname: Moghaddam
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
authors.forename: Aneesh
authors.initials: A
authors.lastname: Alex
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Yearley
authors.forename: Paul
authors.initials: P
authors.lastname: Menard-Katcher
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: Terri
authors.initials: T
authors.lastname: Brown-Whitehorn
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Antonella
authors.initials: A
authors.lastname: Cianferoni
authors.forename: Gary W
authors.initials: GW
authors.lastname: Falk
authors.forename: Mei-Lun
authors.initials: ML
authors.lastname: Wang
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Spergel
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D057765:Eosinophilic Esophagitis / Q000378:metabolism* / Q000473:pathology*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004947:Esophagus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin