RARα Supports the Development of Langerhans Cells and Langerin-expressing Conventional Dendritic Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Sep 27

PMID 30254197

Citations 12

Authors

Seika Hashimoto-Hill

Leon Friesen

SungTae Park

Suji Im

Mark H Kaplan

Chang H Kim

Affiliations

Soon will be listed here.

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 langerinconventional 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.

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