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Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis

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Date
2026-05-08
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Fels Cancer Institute for Personalized Medicine
Subject
Eosinophilic Esophagitis
 Mitochondria
 Interleukins
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https://scholarshare.temple.edu/handle/20.500.12613/11616
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Files for deposit, including: A. Filename: circmtDNA Short description: Patient data for cohort used to assess circulating mitochondria DNA levels along with relevant clinical data used in published article. B. Filename: Mice mtDNA Short description: Murine fold change data for cohort used to assess esophageal mitochondria DNA levels used in published article. C. Filename: MTCO1 Human Cohort Short description: Patient data for cohort used to assess MTCO1 expression in esophageal biopsies along with relevant clinical data used in published article. D. Filename: MTCO1 Mice Cohort Short description: Murine data for cohort used to assess MTCO1 expression in esophageal biopsies along with relevant pathology data used in published article.
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Abstract
Background & aims: Metabolic and mitochondrial dysfunction have recently been implicated in eosinophilic esophagitis (EoE) pathogenesis. However, there is a need to define the influence of EoE-associated inflammatory cues upon mitochondrial biology, mechanisms mediating these effects, and the clinical significance of mitochondrial alterations in EoE. Methods: Mitochondria were evaluated in human biopsies, MC903/ovalbumin-induced murine EoE, and human esophageal keratinocytes stimulated with EoE-relevant cytokines. Mitochondrial mediators were assessed via quantitative reverse transcription polymerase reaction and Western blotting. Metabolism, mitochondrial membrane potential, and apoptosis were measured. Mitochondrial DNA (mtDNA)-encoded genes, ND1 and ND6 were assessed by quantitative polymerase chain reaction in DNA from culture media and circulating nucleic acids from human serum samples. Effects of Janus kinase (JAK) inhibitor ruxolitinib or genetic inhibition of signal transducer and activator of transcription (STAT)3 or STAT6 on mitochondria were assessed in vitro. Results: We identified evidence of increased mitochondria in esophageal mucosa of patients with EoE and mice with EoE-like inflammation. Interleukin (IL)-13 consistently induced mitochondrial accumulation in esophageal keratinocytes in vitro, and this response was associated with increased expression of mediators of mitochondrial biogenesis, fusion, and mitophagy. IL-13 suppressed mitochondrial respiration and adenosine triphosphate (ATP) production, without impacting membrane polarization or apoptosis. Patients with active EoE exhibited elevated serum mtDNA levels and upregulation of mediators of mtDNA-associated inflammatory signaling. Increased mitochondrial mass and accumulation of extracellular mtDNA in IL-13-treated esophageal keratinocytes were dependent on JAK/STAT signaling. Conclusions: We identify IL-13 as a mediator of increased mitochondrial mass in EoE through JAK/STAT signaling. We further demonstrate that IL-13 promotes accumulation of extracellular mtDNA and that circulating mtDNA is elevated in patients with EoE.
Description
Patient and murine data obtained from human serum, human esophageal biopsies and murine biopsies for cohorts used in published article (https://pubmed.ncbi.nlm.nih.gov/41956400/). Description of methods used for collection/generation of data: Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis - PubMed, available at https://pubmed.ncbi.nlm.nih.gov/41956400/. Methods for processing the data: circmtDNA levels and murine mtDNA levels were determined via qPCR. For the circmtDNA cohort, mtDNA copy numbers for genes, ND1 and ND6 were assessed and included in the file. For mice mtDNA levels, ct values for mtDNA gene, mito D-Loop was compared to ct values for nuclear-encoded gene IkkB and fold change values were obtained, which are included in the file. To assess mtDNA levels, primers for mtDNA D-Loop (murine) were used. To assess nuclear DNA, primers for Ikbβ (murine) were used. The relative fold change between the noted mtDNA-encoded genes and nuclear DNA-encoded genes (Ikbβ ) was calculated using the delta-delta CT method. mtDNA copy numbers were evaluated in patient serum samples. Primers for ND6 and ND1 were used. Copy number of each gene was calculated in individual subjects using a standard curve generated for each gene.
Citation
Jackson JL, Saxena R, Murray MG, Staub AJ, Worrell C, Cruz J, Shanas N, Klochkova A, Bordner TH, Crespo JM, Fuller AD, Nazario-Lugo W, Davis G, Golden H, Klein-Szanto AJ, Karakasheva TA, Karami A, Elrod JW, Falk GW, Reichenbach ZW, Ruffner M, Muir AB, Whelan KA. Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis. Dataset. May 8 2026. PMID: 41956400.
Citation to related work
Jackson JL, Saxena R, Murray MG, Staub AJ, Worrell C, Cruz J, Shanas N, Klochkova A, Bordner TH, Crespo JM, Fuller AD, Nazario-Lugo W, Davis G, Golden H, Klein-Szanto AJ, Karakasheva TA, Karami A, Elrod JW, Falk GW, Reichenbach ZW, Ruffner M, Muir AB, Whelan KA. Interleukin-13 Promotes Accumulation of Esophageal Epithelial Mitochondria With Translational Implications for Eosinophilic Esophagitis. Cell Mol Gastroenterol Hepatol. 2026 Apr 27:101782. doi: 10.1016/j.jcmgh.2026.101782. Epub ahead of print. PMID: 41956400.
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