WOFAPS 2025 8th World Congress of Pediatric Surgery

Bin Yang, Heng Guo, Qiang Huang

Xi'an Jiaotong University

Hirschsprung's disease (HSCR) is pathologically defined by distal colonic aganglionosis, resulting in functional intestinal obstruction. Crucially, 30–50% of patients develop life-threatening Hirschsprung-associated enterocolitis (HAEC), the pathogenesis of which remains elusive. Whereas conventional research emphasizes defective neural crest cell migration, accumulating evidence implicates dysregulation of the intestinal immune microenvironment in both HSCR pathogenesis and its complications. Our prior work demonstrates that exogenous CXCL5 attenuates apoptosis in injured enteric neurons, indicative of neuroprotective functions. Paradoxically, CXCL5 functions as a potent neutrophil chemoattractant that is markedly upregulated during inflammatory responses. Macrophages—primary cellular sources of CXCL5—may orchestrate dual pathology through functional polarization (pro-inflammatory M1/anti-inflammatory/reparative M2 phenotypes): their polarization status within the HSRC bowel directly modulates CXCL5 expression, concurrently impairing enteric nervous system development and disrupting local immune homeostasis, thereby potentiating HAEC susceptibility. This study integrates mechanistic interrogation of macrophage polarization-dependent CXCL5 regulation to delineate CXCL5-mediated neuroprotective pathways in enteric neural development, while evaluating how CXCL5 overproduction drives intestinal immune dysregulation and increases HAEC vulnerability, ultimately defining neuro-immune crosstalk in HSCR's core pathology and complications.