Psychological stress induces eosinophils to produce corticotrophin releasing hormone in the intestine

BACKGROUND AND AIMS: Psychological stress plays an important role in an array of intestinal disorders. Corticotrophin releasing hormone (CRH) is involved in the pathogenic process induced by psychological stress. The peripheral sources of CRH remain to be further understood. This paper aims to identify the sources of CRH in the intestine. METHODS AND RESULTS: Mice were treated with chronic restraint stress. A double-labelling approach was taken to localise CRH expression in immune cells (including dendritic cells, mast cells, lymphocytes, enterochromaffin cells and eosinophils) in the intestine by confocal microscopy and flow cytometry. As CRH was identified in eosinophils, a cell line of eosinophil, EoL-1 cells were treated with an array of putative stress mediators. The results showed that substance P (SP) induced the expression/release of CRH in eosinophils via neurokinin receptor 1 and 2. Co-culturing SP-primed eosinophils with the mast cell line, HMC-1 cells, we found that HMC-1 cells were activated by eosinophil-derived CRH that further induced T84 monolayer barrier dysfunction, which was further confirmed by a mouse model study. CONCLUSION: Eosinophils express CRH in the jejunum in response to psychological stress. SP and its receptors mediate the effect of stress in the CRH expression in eosinophils. Eosinophil-derived CRH activates mast cells to induce the jejunum epithelial barrier dysfunction.