title: 1α,25-dihydroxyvitamin D3 (vitamin D3) catalyzes suppressive activity on human natural regulatory T cells, uniquely modulates cell cycle progression, and augments FOXP3.
abstract: Human natural regulatory T cells (nTregs) show great promise for therapeutically modulating immune-mediated disease, but remain poorly understood. One explanation under intense scrutiny is how to induce suppressive function in non-nTregs and increase the size of the regulatory population. A second possibility would be to make existing nTregs more effective, like a catalyst raises the specific activity of an enzyme. The latter has been difficult to investigate due to the lack of a robust short-term suppression assay. Using a microassay described herein we demonstrate that nTregs in distinct phases of cell cycle progression exhibit graded degrees of potency. Moreover, we show that physiological concentrations of 1α,25-dihydroxyvitamin D3 (vitamin D3) boosts nTregs function. The enhanced suppressive capacity is likely due to vitamin D3's ability to uniquely modulate cell cycle progression and elevate FOXP3 expression. These data suggest a role for vitamin D3 as a mechanism for catalyzing potency of nTregs.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Morales-Tirado
authors.forename: David G
authors.initials: DG
authors.lastname: Wichlan
authors.forename: Thasia E
authors.initials: TE
authors.lastname: Leimig
authors.forename: Shayna E A
authors.initials: SE
authors.lastname: Street
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.forename: Janice M
authors.initials: JM
authors.lastname: Riberdy
mesh_terms: D002453:Cell Cycle / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D002762:Cholecalciferol