Science and Research

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

  • Kilic, A.
  • Halu, A.
  • De Marzio, M.
  • Maiorino, E.
  • Duvall, M. G.
  • Bruggemann, T. R.
  • Rojas Quintero, J. J.
  • Chase, R.
  • Mirzakhani, H.
  • Sungur, AÖ
  • Koepke, J.
  • Nakano, T.
  • Peh, H. Y.
  • Krishnamoorthy, N.
  • Abdulnour, R. E.
  • Georgopoulos, K.
  • Litonjua, A. A.
  • Demay, M.
  • Renz, H.
  • Levy, B. D.
  • Weiss, S. T.

Keywords

  • Mice
  • Animals
  • Humans
  • Vitamin D/pharmacology
  • Interleukin-2
  • *Asthma
  • Inflammation
  • Th2 Cells
  • *Vitamin D Deficiency/metabolism
  • *Pneumonia
  • Vitamins
  • asthma
  • genetics
  • genomics
  • human
  • immunology
  • mouse
  • vitamin D receptor
Publication details
DOI: 10.7554/eLife.89270
Journal: Elife
Work Type: Original
Location: UGMLC
Disease Area: AA, PALI
Partner / Member: JLU, UMR
Access-Number: 38567749

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