RDH10, RALDH2, and CRABP2 are required components of PPAR γ-directed ATRA synthesis and signaling in human dendritic cells

Adrienn Gyöngyösi, Istvan Szatmari, Attila Pap, Balazs Dezso, Zoltan Pos, Lajos Széles, Tamas Varga, Laszlo Nagy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

All- trans retinoic acid (ATRA) has a key role in dendritic cells (DCs) and affects T cell subtype specification and gut homing. However, the identity of the permissive cell types and the required steps of conversion of vitamin A to biologically active ATRA bringing about retinoic acid receptor-regulated signaling remains elusive. Here we present that only a subset of murine and human DCs express the necessary enzymes, including RDH10, RALDH2, and transporter cellular retinoic acid binding protein (CRABP)2, to produce ATRA and efficient signaling. These permissive cell types include CD103+ DCs, granulocyte-macrophage colonystimulating factor, and interleukin-4-treated bone marrowderived murine DCs and human monocyte-derived DCs (mo-DCs). Importantly, in addition to RDH10 and RALDH2, CRABP2 also appears to be regulated by the fatty acid-sensing nuclear receptor peroxisome proliferator-activated receptor γ (PPAR γ ) and colocalize in human gut-associated lymphoid tissue DCs. In our model of human mo-DCs, all three proteins (RDH10, RALDH2, and CRABP2) appeared to be required for ATRA production induced by activation of PPARγ and therefore form a linear pathway. This now functionally validated PPARγ-regulated ATRA producing and signaling axis equips the cells with the capacity to convert precursors to active retinoids in response to receptor-activating fatty acids and is potentially amenable to intervention in diseases involving or affecting mucosal immunity.

Original languageEnglish
Pages (from-to)2458-2474
Number of pages17
JournalJournal of Lipid Research
Volume54
Issue number9
DOIs
Publication statusPublished - Sep 1 2013

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Keywords

  • All- trans retinoic acid
  • Cellular retinoic acid binding protein 2
  • INKT cells
  • Lipid antigen presentation
  • Lipid transport
  • Peroxisome proliferator-activated receptor γ
  • Retinoic acid receptor signaling
  • Retinoid metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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