DNGR-1 regulates proliferation and migration of bone marrow dendritic cell progenitors

TL;DR

This study shows that DNGR-1, an immune receptor, influences how dendritic cell progenitors in the bone marrow multiply and migrate to peripheral tissues.

Contribution

The study reveals a novel role for DNGR-1 in regulating cDCpoiesis through cell-intrinsic mechanisms.

Findings

DNGR-1–deficient pre-cDCs show increased proliferation and migration.

DNGR-1 deficiency leads to enhanced colonization of peripheral tissues by cDC progenitors.

DNGR-1 regulates cDCpoiesis via signals from innate immune receptors.

Abstract

Cardoso et al. show that DNGR-1–deficient pre-cDCs display cell-intrinsic alterations in their ability to colonize peripheral organs. Their findings highlight an unexpected role for innate immune receptors in regulating cDCpoiesis.

Conventional dendritic cells (cDCs) are sentinel cells that play a crucial role in both innate and adaptive immune responses. cDCs originate from a progenitor (pre-cDC) in the bone marrow (BM) that travels via the blood to seed peripheral tissues before locally differentiating into functional cDC1 and cDC2 cells, as part of a process known as cDCpoiesis. How cDCpoiesis is regulated and whether this affects the output of cDCs is poorly understood. In this study, we show that DNGR-1, an innate immune receptor expressed by cDC progenitors and type 1 cDCs, can regulate cDCpoiesis in mice. In a competitive chimera setting, cDC progenitors lacking DNGR-1 exhibit increased proliferation and tissue migratory potential. Compared with their WT counterparts, DNGR-1–deficient cDC progenitor cells display superior colonization of peripheral tissues but an altered distribution. These findings suggest that cDCpoiesis can be regulated in part by precursor cell-intrinsic processes driven by signals from innate immune receptors such as DNGR-1 that may respond to alterations in the BM milieu.

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