ArticleScience translational medicine2018
The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.
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Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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71citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% of its field
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.The Journal of allergy and clinical immunology · 2021Pooled it
- Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.The journal of allergy and clinical immunology. In practice · 2024Trial
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- Review
- IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis.JCI insight · 2026Article
- Sexual Dimorphism in Allergic and Mast Cell-Associated Diseases.Clinical reviews in allergy & immunology · 2026Review
- Dupilumab Dampens Mucosal Type 2 Response During Acetylsalicylic Acid Challenge in N-ERD Patients.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Immune functions of the esophagus.The Journal of allergy and clinical immunology · 2026Review
- The Immune Architecture of Eosinophilic Esophagitis: Mechanisms, Therapeutic Targets, and Precision Management.ImmunoTargets and therapy · 2026Review
- Comparative Transcriptomics Reveals a Dual Role of the Epidermal Differentiation Complex in the Skin and the Oesophagus.Experimental dermatology · 2025Article
- The oesophagus as an immune organ.Nature reviews. Gastroenterology & hepatology · 2025Review
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Overlap of Genomic and Transcriptomic Genes Identified in Familial Eosinophilic Esophagitis.Gastroenterology · 2025Article
- The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.Clinical and translational medicine · 2025Article
- Unravelling the pathogenesis of Eosinophilic Esophagitis from genetic predisposition to environmental triggers.Clinical and experimental immunology · 2025Review
- Eosinophilic Esophagitis and Cow's Milk: Mechanisms, Challenges, and Treatment Perspectives.Nutrients · 2025Review
- Vascular endothelial growth factor A inhibition remodels the transcriptional signature of lipid metabolism in psoriasis non-lesional skin in 12 h ex vivo culture.Skin health and disease · 2024Article
- Advances in omics data for eosinophilic esophagitis: moving towards multi-omics analyses.Journal of gastroenterology · 2024Review
- Article
- Eosinophilic Esophagitis and Inflammatory Bowel Disease: What Are the Differences?International journal of molecular sciences · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 1 institution in 2 countries.
Nurit P AzouzDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0003-4969-1263
Mario A Ynga-DurandDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0002-8586-3993
Julie M CaldwellDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0002-3855-299X
Ayushi JainDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0002-9672-6003
Mark RochmanDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0002-0818-927X
Demetria M FischesserDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0001-8897-830X
Leanne M RayDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Mary C BedardDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Melissa K MinglerDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Carmy ForneyCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Matthew EilermanDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0002-7865-9927
Jonathan T KuhlDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Hua HeDivision of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Jocelyn M Biagini MyersDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Vincent A MukkadaDivision of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Philip E PutnamDivision of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Gurjit K Khurana HersheyDivision of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0001-6663-977X
Leah C KottyanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0003-3979-2220
Ting WenDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.
Lisa J MartinDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.ORCID 0000-0001-8702-9946
Marc E RothenbergDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA. rothenberg@cchmc.org.ORCID 0000-0001-9790-6332
Cincinnati Children's Hospital Medical Center · US
Funding
LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI MEINZEN-DERR, JAREEN, STRAWN, JEFFREY ROBERT · 2015 to 2024
$37.5MTSLP, IL-9-producing mucosal mast cells, and allergic inflammationU19AI070235 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI Gurjit K. Khurana Hershey · 2006 to 2026
$31.3MStem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4MTRAINING (CAREER DEVELOPMENT) COMPONENTU54AI117804 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI GLENN T FURUTA, Marc E. Rothenberg · 2014 to 2026
$18.5MTissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Grant Sanford Schulert · 2016 to 2026
$7.7MRegulation of Gastrointestinal EosinophilsR37AI045898 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI ROTHENBERG, MARC E. · 2010 to 2019
$3.6MShort Term Medical Student Training GrantT35DK060444 · NIDDK · UNIVERSITY OF CINCINNATI · PI JASON T BLACKARD · 2002 to 2026
$2.3MMechanisms of genetic risk at 2p23 in Eosinophilic EsophagitisR01DK107502 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTYAN, LEAH CLAIRE · 2016 to 2020
$1.8MEosinophil, Chemokine and IL-13 Cooperativity in AsthmaR01AI057803 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI ROTHENBERG, MARC E. · 2004 to 2007
$731kNCATS NIH HHS UL1 TR001425NIAID NIH HHS R01 AI057803NIAID NIH HHS R37 AI045898NIAID NIH HHS U19 AI070235NIAID NIH HHS U54 AI117804NIAMS NIH HHS P30 AR070549NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK107502NIDDK NIH HHS T35 DK060444
Abstract
Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing
Indexed as
BiomarkersCell DifferentiationCRISPR-Cas SystemsCytokinesEosinophilic EsophagitisEosinophilsEpistasis, GeneticEpithelial CellsEpithelial-Mesenchymal TransitionEsophagusFilaggrin ProteinsGene Expression RegulationGene SilencingHumansInflammationInflammation MediatorsBiomarkersCytokinesFilaggrin ProteinsFLG protein, humanInflammation MediatorsInterleukin-13Receptors, Urokinase Plasminogen ActivatorSerine Peptidase Inhibitor Kazal-Type 5Serine Peptidase Inhibitors, Kazal TypeSPINK5 protein, humanSPINK7 protein, humanThymic Stromal LymphopoietinUrokinase-Type Plasminogen ActivatorVimentin
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.