期刊
NATURE MEDICINE
卷 19, 期 8, 页码 1005-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3281
关键词
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资金
- US National Institutes of Health [AI061570, AI087990, AI074878, AI095776, AI102942, AI095466, AI09560, AI097333, T32-AI060516, F32-AI098365, T32-AR007465, KL2-RR024132, F32-AI085828, AI091759, K08-AI089982, R00EB010071]
- Swiss National Science Foundation Prospective and Advanced Research Fellowships [PBBEP3_130438, PA00P3_136468]
- Australian National Health and Medical Research Council Overseas Biomedical Fellowship [613718]
- State of Pennsylvania [SAP 4100042728]
- Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award
- Crohn's and Colitis Foundation of America
- US National Institutes of Health/US National Institute of Diabetes and Digestive and Kidney Diseases P30 Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]
- Joint Penn-Children's Hospital of Philadelphia Center in Digestive, Liver and Pancreatic Medicine
- US National Cancer Institute Comprehensive Cancer Center [P30-CA016520]
- Skin Disease Research Center [P30-AR057217]
- Electron Microscopy Resource Laboratory
- Children's Hospital of Philadelphia Institutional Development Fund
- US Department of Defense [A-16809.2]
- Abbot Nutrition [ANUS1013]
- Lehigh University start-up fund
- Institute for Translational Medicine and Therapeutics Transdisciplinary Program in Translational Medicine and Therapeutics (from the US National Center for Research Resources) [UL1-RR024134]
- Ruiz at eBioscience for samples of flow cytometry reagents for human basophil panel development
- Grants-in-Aid for Scientific Research [24390093] Funding Source: KAKEN
- Medical Research Council [G0000635] Funding Source: researchfish
- Swiss National Science Foundation (SNF) [PBBEP3_130438, PA00P3_136468] Funding Source: Swiss National Science Foundation (SNF)
- MRC [G0000635] Funding Source: UKRI
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.
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