title: Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Respirology, The First Hospital, Shanxi Medical University, Taiyuan, China.
authors.forename: Huan-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Yang
authors.affiliation: Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Geng
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Bai-Sui
authors.initials: BS
authors.lastname: Feng
authors.affiliation: Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen, China.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000077465:Cabergoline; D003092:Colitis / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018928:Immunity, Mucosal / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism / Q000523:psychology; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D011388:Prolactin; D016264:Dextran Sulfate; D000077465:Cabergoline
keywords: INFLAMMATION