Journal Article

TSLP-elicited basophil responses can mediate the pathogenesis of eosinophilic esophagitis

Muir, Amanda B., Yearley, Jennifer H., Menard-Katcher, Paul, Sattentau, Quentin J., Nair, Meera G., Benitez, Alain J., Kim, Brian S., Kubo, Masato, Hakonarson, Hakon, Obata-Ninomiya, Kazushige, Brown-Whitehorn, Terri, Sleiman, Patrick M., Wang, Mei-Lun, Artis, David, Ruymann, Kathryn R., Chikwava, Kudakwashe R., Tait Wojno, Elia D., Siracusa, Mark C., Cianferoni, Antonella, Noti, Mario, Moghaddam, Amin E., Zhou, Chao, Karasuyama, Hajime, Falk, Gary W., de Waal Malefyt, Rene, Giacomin, Paul R., Alex, Aneesh, Spergel, Jonathan M., Comeau, Michael R., Hill, David A.

2013

Overview

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent 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 remains unknown. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE but was dependent on TSLP-elicited basophils. Therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. Critically, in human subjects with EoE, we observed elevated TSLP levels and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses. Together, these data suggest that the TSLP-basophil axis could be therapeutically targeted to treat EoE.