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Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation
  1. Wei Wu1,
  2. Mingming Sun1,
  3. Huan-Ping Zhang2,
  4. Tengfei Chen1,
  5. Ruijin Wu1,
  6. Changqin Liu1,
  7. Gui Yang3,
  8. Xiao-Rui Geng3,
  9. Bai-Sui Feng1,
  10. Zhigang Liu4,
  11. Zhanju Liu1,
  12. Ping-Chang Yang4
  1. 1Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China
  2. 2Department of Respirology, The First Hospital, Shanxi Medical University, Taiyuan, China
  3. 3Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen, China
  4. 4Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen, China
  1. Correspondence to Dr Pingchang Yang, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Room 204 of the Medical School Building; 3688 Nanhai Ave., Shenzhen 518060, China; pcy2356{at}szu.edu.cn and Dr Zhanju Liu, Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China; liuzhanju88{at}163.com

Abstract

Objective The dysfunction of immune regulation plays a critical role in the pathogenesis of a number of chronic inflammatory disorders, such as IBD. A close relationship between psychological stress and intestinal inflammation has been noted; the underlying mechanism remains elusive. This study aims to elucidate a pathological pathway between psychological stress and the dysfunction of regulatory T cells (Treg), and its effect on facilitating intestinal inflammation.

Design A restraint stress model was employed to induce psychological stress in mice. The functions of Tregs were determined by assessing the immune suppressor effects in the intestine. A mouse model of intestinal inflammation was established using a low dose of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) together with the challenge of chronic stress.

Results After treating mice with restraint stress, the suppressor function of intestinal Treg was compromised, although the frequency of Treg was not changed in the intestine. Further observation revealed that stress induced Tregs in the intestine to differentiate into foxhead box P3+ interleukin (IL)-17+ tumour necrosis factor (TNF)-α+ T cells. We also observed that exposure to stress-derived prolactin induced dendritic cells (DC) to produce IL-6 and IL-23 in vitro and in vivo, which played a critical role in altering Treg's phenotypes. Treating mice with chronic stress facilitated the initiation of intestinal inflammation by a low dose of TNBS or DSS, which was abolished by pretreatment with an inhibitor of prolactin, the cabergoline.

Conclusions Psychological stress-derived prolactin alters DC and Treg's properties to contribute to intestinal inflammation.

  • INFLAMMATION

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