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The following is a summary of “IL-13–induced STAT3-dependent signaling networks regulate esophageal epithelial proliferation in eosinophilic esophagitis,” published in the DECEMBER 2023 issue of Allergy & Immunology by Marella, et al.

Eosinophilic esophagitis (EoE) is associated with basal zone hyperplasia (BZH) and dilated intercellular spaces (DISs), contributing to its clinical manifestations. However, the molecular pathways underlying BZH remain largely unexplored. For a study, researchers sought to elucidate the role of IL–13–induced transcriptional programs in esophageal epithelial proliferation in EoE.

Various analyses, including RNA sequencing, bioinformatics, Western blot, reverse transcriptase quantitative PCR, and histologic assessments, were conducted on esophageal biopsies from healthy individuals and patients with EoE. Primary esophageal cells from patients with EoE and IL-13–stimulated esophageal epithelial keratinocytes (EPC2-ALI) were also examined. Genetic and pharmacologic approaches, along with an in vivo IL-13–induced esophageal epithelial remodeling model, were employed to investigate the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6, as well as secreted frizzled-related protein 1 (SFRP1) in esophageal epithelial proliferation.

RNA sequencing identified 82 common differentially expressed genes enriched for putative STAT3 target genes in esophageal biopsies and EPC2-ALI. In vitro and in vivo analyses revealed a connection between IL-13–induced STAT3 and STAT6 phosphorylation, SFRP1 mRNA expression, and esophageal epithelial proliferation. STAT3-dependent IL-13–induced esophageal epithelial proliferation was regulated by the STAT3 target SFRP1. SFRP1 mRNA was elevated in biopsies from active EoE patients, identifying a unique SFRP1<sup style=”vertical-align: sup;”>+</sup> esophageal epithelial cell subpopulation expressing core EoE proinflammatory transcriptome genes (CCL26, ALOX15, CAPN14, ANO1, and TNFAIP6).

The study identified SFRP1 as a crucial regulator of IL-13–induced and STAT3-dependent esophageal proliferation and BZH in EoE. It establishes a link between SFRP1⁺ esophageal epithelial cells and the proinflammatory and epithelial remodeling response in EoE.

Source: jacionline.org/article/S0091-6749(23)01100-4/fulltext