Expression of transforming growth factor β1, transforming growth factor type I and II receptors, and TNF-α in the mucosa of the small intestine in infants with food protein-induced enterocolitis syndrome

Background. TNF-alpha secreted by activated T cells is known to increase intestinal permeability whereas transforming growth factor (TGF) beta has the ability to protect the epithelial barrier. Objective: We determined the expression of TGF-beta1, its receptors, and TNF-alpha on the mucosa of small intestine to investigate their roles in the pathogenesis of food protein-induced enterocolitis syndrome (FPIES). Methods: Twenty-eight infants diagnosed with FPIES by means of clinical criteria and challenge test results were included. Immunohistochemical stains for TGF-beta1, type I and 2 TGF-beta receptors, and TNF-alpha on duodenal biopsy specimens were performed. Results: TGF-beta1 expression was generally depressed in patients. Expression of type I TGF-beta receptor was significantly lower in the patients who had villous atrophy compared with expression in those patients who did not (P < .001) and negatively correlated with the severity of atrophy (r = -0.59, P < .001). Expression of type 2 TGF-beta receptor showed no significant difference between the patients with or without villous atrophy. The immunoreactivity for both TGF-beta receptors on lamina proprial cells was slight or negative. TNF-alpha expression was detected on both epithelial and lamina proprial cells and was significantly greater in the patients who had villous atrophy compared with that in the patients who did not (P < .01). Conclusion: Our results suggest that decreased countering activity of TGF-beta1 against T-cell cytokines is implicated in the pathogenesis of FPIES. The significantly lower expression of type 1 TGF-beta receptor compared with type 2 receptor suggests the differential contribution of each receptor to the diverse biologic activities of TGF-beta in the intestinal epithelium.