Vitamin D Regulates the Microbiota to Control the Numbers of RORγt/FoxP3+ Regulatory T Cells in the Colon

Front Immunol. 2019 Jul 30:10:1772. doi: 10.3389/fimmu.2019.01772. eCollection 2019.

Abstract

The active form of vitamin D (1,25(OH)2D) suppresses experimental models of inflammatory bowel disease in part by regulating the microbiota. In this study, the role of vitamin D in the regulation of microbe induced RORγt/FoxP3+ T regulatory (reg) cells in the colon was determined. Vitamin D sufficient (D+) mice had significantly higher frequencies of FoxP3+ and RORγt/FoxP3+ T reg cells in the colon compared to vitamin D deficient (D-) mice. The higher frequency of RORγt/FoxP3+ T reg cells in D+ colon correlated with higher numbers of bacteria from the Clostridium XIVa and Bacteroides in D+ compared to D- cecum. D- mice with fewer RORγt/FoxP3+ T reg cells were significantly more susceptible to colitis than D+ mice. Transfer of the cecal bacteria from D+ or D- mice to germfree recipients phenocopied the higher numbers of RORγt/FoxP3+ cells and reduced susceptibility to colitis in D+ vs. D- recipient mice. 1,25(OH)2D treatment of the D- mice beginning at 3 weeks of age did not completely recover RORγt/FoxP3+ T reg cells or the Bacteriodes, Bacteriodes thetaiotaomicron, and Clostridium XIVa numbers to D+ values. Early vitamin D status shapes the microbiota to optimize the population of colonic RORγt/FoxP3+ T reg cells important for resistance to colitis.

Keywords: T regulatory (T reg) cells; gnotobiotic mice; inflammatory bowel diseases; microbiota; vitamin D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteroidetes / immunology
  • Calcitriol / pharmacology*
  • Clostridium / immunology
  • Colitis* / immunology
  • Colitis* / microbiology
  • Colitis* / pathology
  • Colon* / immunology
  • Colon* / microbiology
  • Colon* / pathology
  • Forkhead Transcription Factors / immunology
  • Gastrointestinal Microbiome* / drug effects
  • Gastrointestinal Microbiome* / immunology
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse
  • Calcitriol