For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.

TitleThymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
Publication TypeJournal Article
Year of Publication2013
AuthorsNoti M, Wojno EDTait, Kim BS, Siracusa MC, Giacomin PR, Nair MG, Benitez AJ, Ruymann KR, Muir AB, Hill DA, Chikwava KR, Moghaddam AE, Sattentau QJ, Alex A, Zhou C, Yearley JH, Menard-Katcher P, Kubo M, Obata-Ninomiya K, Karasuyama H, Comeau MR, Brown-Whitehorn T, Malefyt Rde Waal, Sleiman PM, Hakonarson H, Cianferoni A, Falk GW, Wang M-L, Spergel JM, Artis D
JournalNat Med
Volume19
Issue8
Pagination1005-13
Date Published2013 Aug
ISSN1546-170X
KeywordsAdult, Animals, Antibodies, Monoclonal, Basophils, Cytokines, Disease Models, Animal, Eosinophilic Esophagitis, Eosinophils, Esophagus, Female, Humans, Immunoglobulin E, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neutralization Tests
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.

DOI10.1038/nm.3281
Alternate JournalNat. Med.
PubMed ID23872715
PubMed Central IDPMC3951204
Grant ListAI061570 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI091759 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI09560 / AI / NIAID NIH HHS / United States
AI095776 / AI / NIAID NIH HHS / United States
AI097333 / AI / NIAID NIH HHS / United States
AI102942 / AI / NIAID NIH HHS / United States
F32 AI085828 / AI / NIAID NIH HHS / United States
F32 AI098365 / AI / NIAID NIH HHS / United States
F32-AI085828 / AI / NIAID NIH HHS / United States
F32-AI098365 / AI / NIAID NIH HHS / United States
K08 AI089982 / AI / NIAID NIH HHS / United States
K08-AI089982 / AI / NIAID NIH HHS / United States
KL2-RR024132 / RR / NCRR NIH HHS / United States
P30 AR057217 / AR / NIAMS NIH HHS / United States
P30-AR057217 / AR / NIAMS NIH HHS / United States
P30-CA016520 / CA / NCI NIH HHS / United States
P30-DK050306 / DK / NIDDK NIH HHS / United States
R00 EB010071 / EB / NIBIB NIH HHS / United States
R00EB010071 / EB / NIBIB NIH HHS / United States
R01 AI091759 / AI / NIAID NIH HHS / United States
R01 AI097333 / AI / NIAID NIH HHS / United States
R01 DK087789 / DK / NIDDK NIH HHS / United States
T32-AI060516 / AI / NIAID NIH HHS / United States
T32-AR007465 / AR / NIAMS NIH HHS / United States
UL1-RR024134 / RR / NCRR NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587