T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism

Kristina Edfeldt, Philip T Liu, Rene Chun, Mario Fabri, Mirjam Schenk, Matthew Wheelwright, Caroline Keegan, Stephan R Krutzik, John S Adams, Martin Hewison, Robert L Modlin

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)


We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.

Original languageEnglish
Pages (from-to)22593-8
Number of pages6
JournalNational Academy of Sciences. Proceedings
Issue number52
Publication statusPublished - 28 Dec 2010


  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Antimicrobial Cationic Peptides
  • Blotting, Western
  • Calcitriol
  • Cells, Cultured
  • Cytokines
  • Gene Expression
  • Humans
  • Interferon-gamma
  • Interleukin-4
  • Monocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Steroid Hydroxylases
  • T-Lymphocytes
  • Th1 Cells
  • Th2 Cells
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Vitamin D
  • Vitamin D3 24-Hydroxylase
  • beta-Defensins


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