IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis

Nurit P. Azouz; Andrea M. Klingler; Sierra S. Beach; Kalen A. Rossey; Mark Rochman; Misu Paul; Julie M. Caldwell; Michael Brusilovsky; Alexander T. Dwyer; Xiaoting Chen; Daniel Miller; Carmy Forney; Leah C. Kottyan; Matthew T. Weirauch; Marc E. Rothenberg

doi:10.1172/jci.insight.204687

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Azouz, N. in: PubMed | Google Scholar |

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Klingler, A. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Beach, S. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Rossey, K. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Rochman, M. in: PubMed | Google Scholar |

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Paul, M. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Caldwell, J. in: PubMed | Google Scholar |

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Brusilovsky, M. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Dwyer, A. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Chen, X. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Miller, D. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Forney, C. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Kottyan, L. in: PubMed | Google Scholar |

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Weirauch, M. in: PubMed | Google Scholar

¹Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

Find articles by Rothenberg, M. in: PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.204687.
Copyright © 2026, Azouz et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published April 28, 2026 - Version history

Eosinophilic esophagitis (EoE) is a type 2 allergic disease characterized by esophageal inflammation and epithelial cell dysfunction. The acquired loss of the anti-serine protease of kazal type 7 (SPINK7) in the squamous epithelium of the esophagus has a causal role in EoE pathogenesis. Yet there is a limited understanding of the factors that regulate its expression and responsiveness to inflammatory stimuli. Herein, we have identified the transcription factor, ovo like transcriptional repressor 1 (OVOL1) as an esophageal selective gene product that regulates SPINK7 promoter activity. Overexpression of OVOL1 increased SPINK7 expression, whereas its depletion decreased SPINK7 expression, impaired epithelial barrier and increased production of the pro-atopy cytokine thymic stromal lymphopoietin (TSLP). Stimulation with IL-13 abrogated the nuclear translocation of OVOL1 and promoted enhanced degradation of OVOL1 protein. This effect of IL-13 was dependent on the esophageal specific cysteine protease calpain-14 at least in part. Analysis of human esophageal biopsies demonstrated that the expression of esophageal OVOL1 correlated with SPINK7 transcript expression and was lost as a function of EoE disease activity. In summary, our study identifies key regulatory mechanisms in EoE pathogenesis, demonstrating that OVOL1 promotes SPINK7 transcription, whereas IL-13 suppresses this pathway in EoE.

Version 1 (April 28, 2026): In-Press Preview

IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis

Nurit P. Azouz,¹ Andrea M. Klingler,¹ Sierra S. Beach,¹ Kalen A. Rossey,¹ Mark Rochman,¹ Misu Paul,¹ Julie M. Caldwell,¹ Michael Brusilovsky,¹ Alexander T. Dwyer,¹ Xiaoting Chen,¹ Daniel Miller,¹ Carmy Forney,¹ Leah C. Kottyan,¹ Matthew T. Weirauch,¹ and Marc E. Rothenberg¹

Article tools

Metrics

Go to

IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis

Nurit P. Azouz,1 Andrea M. Klingler,1 Sierra S. Beach,1 Kalen A. Rossey,1 Mark Rochman,1 Misu Paul,1 Julie M. Caldwell,1 Michael Brusilovsky,1 Alexander T. Dwyer,1 Xiaoting Chen,1 Daniel Miller,1 Carmy Forney,1 Leah C. Kottyan,1 Matthew T. Weirauch,1 and Marc E. Rothenberg1

Article tools

Metrics

Go to

Sign up for email alerts

Nurit P. Azouz,¹ Andrea M. Klingler,¹ Sierra S. Beach,¹ Kalen A. Rossey,¹ Mark Rochman,¹ Misu Paul,¹ Julie M. Caldwell,¹ Michael Brusilovsky,¹ Alexander T. Dwyer,¹ Xiaoting Chen,¹ Daniel Miller,¹ Carmy Forney,¹ Leah C. Kottyan,¹ Matthew T. Weirauch,¹ and Marc E. Rothenberg¹