title: Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells.
abstract: OBJECTIVE
  Regulatory T cells (Treg) are critical regulators of asthma. Crocetin is isolated from Chinese herb saffron and is a natural carotenoid dicarboxylic acid with anti-inflammatory potential. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied.
  
  
  METHODS
  We used Crocetin to treat mice with established ovalbumin (OVA)-induced asthma. We purified CD4+CD25+ Treg cells by flow cytometry and analyzed the levels of two immunoregulatory proteins Foxp3 and tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in Treg cells. We depleted either Foxp3 or TIPE2 in mouse lung through lentivirus-mediated delivery of shRNA, and analyzed their effects on severity of asthma and Treg cells after Crocetin treatment.
  
  
  RESULTS
  Crocetin treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice. Moreover, Crocetin significantly increased the levels of TIPE2 and Foxp3 in Treg cells and the number of Treg cells. Depletion of Foxp3 abolished the increased in Treg cells, and the effects of Crocetin on the severity of asthma, without affecting TIPE2 levels in Treg cells. On the other hand, depletion of TIPE2 abolished both the increased in Treg cells and the effects of Crocetin on the severity of asthma, through suppressing Foxp3.
  
  
  CONCLUSIONS
  Crocetin may activate Foxp3 through TIPE2 in asthma-associated Treg cells to mitigate the severity of asthma.
authors.forename: Jurong
authors.initials: J
authors.lastname: Ding
authors.forename: Jianhua
authors.initials: J
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002338:Carotenoids / Q000494:pharmacology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C552057:TNFAIP8L2 protein, human; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids