CD4+/IL-4+ lymphocytes of the lamina propria and substance P promote colonic protection during acute stress

Ivonne Maciel Arciniega-Martínez, Aldo Arturo Reséndiz Albor, Luz María Cárdenas Jaramillo, Juan Manuel Gutiérrez-Meza, Ramcés Falfán-Valencia, Belen Mendoza Arroyo, Mariazell Yépez-Ortega, Judith Pacheco-Yépez, Edgar Abarca-Rojano

Research output: Contribution to journalArticlepeer-review


Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus-pituitary-adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine-producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonu- clear, goblet and mast cells, a decrease in claudin-1 expression and an elevation in E-cadherin expression during acute stress. Increased E-cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti-inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL-6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.

Original languageEnglish
Article number63
JournalMolecular Medicine Reports
Issue number2
StatePublished - Feb 2022


  • Acute stress
  • CD4/IL-4 lymphocytes
  • Chronic stress
  • Colon
  • Goblet cells
  • Intestine
  • Mast
  • Substance P


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