Thymic stromal lymphopoietin–elicited basophil responses promote eosinophilic esophagitis

Noti, Mario, Tait Wojno, Elia D., Kim, Brian S., Siracusa, Mark C., Giacomin, Paul R., Nair, Meera G., Benitez, Alain J., Ruymann, Kathryn R., Muir, Amanda B., Hill, David A., Chikwava, Kudakwashe R., Moghaddam, Amin E., Sattentau, Quentin J., Alex, Aneesh, Zhou, Chao, Yearley, Jennifer H., Menard-Katcher, Paul, Kubo, Masato, Obata-Ninomiya, Kazushige, Karusuyama, Hajime, Comeau, Michael R., Brown-Whitehorn, Terri, de Waal Malefyt, Rene, Sleiman, Patrick M., Hakonarson, Hakon, Cianferoni, Antonella, Falk, Gary W., Wang, Mei-Lun, Spergel, Jonathan M., and Artis, David (2013) Thymic stromal lymphopoietin–elicited basophil responses promote eosinophilic esophagitis. Nature Medicine, 19 (8). pp. 1005-1013.

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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.

Item ID: 27749
Item Type: Article (Research - C1)
ISSN: 1546-170X
Date Deposited: 22 Jul 2013 01:40
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110701 Allergy @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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