RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells

Seika Hashimoto-Hill, Leon Friesen, Sungtae Park, Suji Im, Mark Kaplan, Chang H. Kim

Research output: Contribution to journalArticle

Abstract

Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin+conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPβ. RARα promotes the development of LCs and langerin+ conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.

Original languageEnglish (US)
Article number3896
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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Retinoic Acid Receptors
Langerhans Cells
Dendritic Cells
Tretinoin
acids
cells
direct current
Thromboplastin
Dermis
Epidermis
Embryonic Development
Cell Differentiation
Bone
Transcription Factors
Bone Marrow
Retinoic Acid Receptor alpha
epidermis
Tissue
bone marrow
Population

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells. / Hashimoto-Hill, Seika; Friesen, Leon; Park, Sungtae; Im, Suji; Kaplan, Mark; Kim, Chang H.

In: Nature Communications, Vol. 9, No. 1, 3896, 01.12.2018.

Research output: Contribution to journalArticle

Hashimoto-Hill, Seika ; Friesen, Leon ; Park, Sungtae ; Im, Suji ; Kaplan, Mark ; Kim, Chang H. / RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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