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

Seika Hashimoto-Hill, Leon Friesen, Sungtae Park, Suji Im, Mark H. Kaplan and Chang H. Kim ()
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Seika Hashimoto-Hill: Purdue University
Leon Friesen: Purdue University
Sungtae Park: Purdue University
Suji Im: Purdue University
Mark H. Kaplan: Indiana University School of Medicine
Chang H. Kim: University of Michigan Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06341-8

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DOI: 10.1038/s41467-018-06341-8

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