The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing

Ian Topilski, Liat Flaishon, Yaron Naveh, Alon Harmelin, Yoram Levo, Idit Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

The fat soluble vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH 2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH 2D3 has anti-inflammatory effects in an in vivo Th2-dependent asthma model. In addition, we demonstrate that 1,25(OH 2D3 down-regulates the cytoskeleton rearrangement required for promoting integrin-mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine-induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)2D3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.

Original languageEnglish
Pages (from-to)1068-1076
Number of pages9
JournalEuropean Journal of Immunology
Volume34
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Keywords

  • Asthma
  • CD4 T cells
  • Cytoskeleton rearrangement
  • Migration
  • Th2 cells
  • Vitamin D

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