title: Type I interferons maintain Foxp3 expression and T-regulatory cell functions under inflammatory conditions in mice.
abstract: OBJECTIVE
  Foxp3(+) T-regulatory cells (Tregs) maintain intestinal homeostasis under conditions of continuous challenge with inflammatory microbes. However, plasticity of the Treg population under certain conditions has been reported; Foxp3(+) Tregs can be converted to Foxp3(-) CD4(+) T cells.
  
  
  METHODS
  We used mice with a T cell-induced colitis model to study the regulatory role of type I interferons (IFNs) in adaptive immunity. We transferred CD4(+)CD45RB(hi) (RB(hi)) T cells, with or without CD4(+)CD45RB(lo) CD25(+) T cells, from wild-type or IFN-αβR(-/-) mice into Rag1(-/-) recipients. We analyzed induction of colitis by flow cytometry, confocal microscopy, and enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction analyses. IFN-αβR(-/-)Rag(-/-) mice were given injections of recombinant IFN-α following transfer of IFN-αβR(-/-) RB(hi) T cells and CD4(+)Foxp3(+) cells from Foxp3-eGFP mice.
  
  
  RESULTS
  Signaling by type I IFNs was required for maintenance of Foxp3 expression and the suppressive activity of Tregs in mice. Transfer of CD4(+)CD45RB(lo)CD25(+) Tregs from IFN-αβR(-/-) mice did not prevent T-cell induction of colitis in mice. Foxp3 expression by Tregs transferred from IFN-αβR(-/-) mice was significantly lower than that of Tregs from wild-type mice. Administration of recombinant IFN-α reduced T cell-mediated colitis by increasing the number of Foxp3(+) Tregs and their suppressive functions.
  
  
  CONCLUSIONS
  Type I IFNs regulate intestinal homeostasis by maintaining Foxp3 expression on Tregs in colons of mice under inflammatory conditions.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA. selee@chonnam.ac.kr
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Xiangli
authors.initials: X
authors.lastname: Li
authors.forename: Joanna C K
authors.initials: JC
authors.lastname: Kim
authors.forename: Jongdae
authors.initials: J
authors.lastname: Lee
authors.forename: Jose M
authors.initials: JM
authors.lastname: González-Navajas
authors.forename: Seol Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
authors.forename: Eyal
authors.initials: E
authors.lastname: Raz
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003092:Colitis / Q000276:immunology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007370:Interferon Type I