Photo Credit: Md Ariful Islam
The following is a summary of “Eosinophilic Esophagitis Drives Tissue Fibroblast Regenerative Programs Towards Pathologic Dysfunction,” published in the November 2024 issue of Allergy and Immunology by Jumabay et al.
Eosinophilic esophagitis (EoE) causes tissue remodeling, fibrosis, and esophageal rigidity. The molecular mechanisms driving these complications are still under investigation. Understanding fibroblast dysfunction in EoE may offer new therapeutic targets.
Researchers conducted a retrospective study to investigate the impact of chronic EoE inflammation on fibroblast dysfunction.
They used single-cell RNA sequencing (scRNA-Seq), fluorescence-activated cell sorting (FACS), and fibroblast differentiation and migration assays to decipher induced and retained pathogenic dysfunctions in EoE versus healthy esophageal fibroblasts.
The results showed that EoE fibroblasts retained regenerative programs for rigid cells such as chondrocytes (P<0.05) but lost the ability to differentiate into soft cells like adipocytes (P<0.01), as observed in biopsy immunostaining (P<0.01). EoE fibroblasts displayed pro-inflammatory and pro-rigidity transcriptional programs on scRNA-Seq. In vivo, regenerative fibroblasts exhibited increased migration in EoE (P<0.01). Flow analysis and functional assays showed reduced surface CD73 expression and activity in EoE fibroblasts (P<0.05), suggesting impaired ATP handling. EoE fibroblast dysfunctions were induced in healthy fibroblasts by lowering CD73 activity and rescued with adenosine repletion.
Investigators concluded that normalizing extracellular ATP handling and CD73 could improve pathogenic fibroblast dysfunction and enhance tissue regeneration in type 2 inflammatory diseases.
Source: jacionline.org/article/S0091-6749(24)01280-6/abstract
