CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection

Background & Aims: Enterochromaffin (EC) cells are dispersed throughout the gastrointestinal (GI) mucosa and are the main source of 5-hydroxytryptamine (5-HT) in the gut. 5-HT has been implicated in the pathophysiology of a number of GI disorders but the mechanisms regulating the 5-HT production in the gut are unknown. This study investigated the role of CD4 + T cells in 5-HT production using a model of enteric parasitic infection. Methods & Results: Severe combined immune deficiency (SCID) mice and their wild-type controls were infected with nematode, Trichuris muris and euthanized on various days post-infection to study colonic EC cells and 5-HT. The number of EC cells and 5-HT were significantly higher in infected wild-type mice compared to non-infected mice. EC cells numbers and 5-HT amount were significantly lower in SCID mice after infection as compared to wild-type mice. Numbers of EC cells and 5-HT amount significantly increased following reconstitution of SCID mice with CD4 + T cells from infected mice and this was accompanied by an up-regulation of colonic CD3 + T cells and Th2 cytokines. Laser capture microdissection based molecular and immunofluorescence techniques revealed the presence of the IL-13 receptor a1-chain on EC cell. Conclusion: These results demonstrate an important immuno-endocrine axis in the gut, where secretory products from CD4 + T cells interact with EC cells to enhance 5-HT production in the gut via Th2 based mechanisms. These results demonstrate new insights into the mechanisms of gut function which may ultimately lead to improved therapeutic strategies in GI functional and inflammatory disorders.