Differential chemokine receptor expression and usage by pre-cDC1 and pre-cDC2

Differential chemokine receptor expression and usage by pre-cDC1 and pre-cDC2.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/imcb.12186
Journal or Publication Title: Immunology and Cell Biology
Volume: 96
Number: 10
Page Range: pp. 1131-1139
Date: 2018
Divisions: Epigenetics and RNA Biology
Immune Imaging
Liver Enzymes in Metabolism and Inflammation
Depositing User: General Admin
Identification Number: 10.1111/imcb.12186
ISSN: 08189641
Date Deposited: 03 Jan 2021 22:32

Conventional dendritic cells (cDCs) are continuously replenished by bone marrow-derived precursors called pre-DCs, which traffic through the blood to peripheral tissues. Pre-DCs are a heterogeneous population that includes cDC subset-committed progenitors, namely pre-cDC1 and pre-cDC2, which give rise to mature cDC1 and cDC2, respectively. Regulation of pre-DC subset trafficking is thought to aid the host response to immune challenge. However, the molecular cues regulating pre-cDC1 versus pre-cDC2 trafficking toward peripheral sites during homeostasis and disease remain elusive. Here, we report that pre-cDC1 but not pre-cDC2 express the T helper type 1-associated chemokine receptor CXCR3. Moreover, we identify a cell-intrinsic role for CXCR3 in the trafficking of pre-cDC1 to melanoma tumors but not to non-inflamed organs. We also show that tumor cDC1 numbers can be increased pharmacologically by targeting dipeptidyl peptidase-4 (CD26), a negative regulator of CXCR3 ligands. Our findings demonstrate that pre-cDC1 trafficking is regulated distinctly from pre-cDC2, which is relevant for our understanding of the DC lineage in the context of cancer and inflammation.

Keywords: CXCR3; Chemokine receptors; dendritic cells; melanoma; pre-cDC1; pre-cDC2; trafficking.

© 2018 Australasian Society for Immunology Inc.

Cook, Stuart J
Lee, Quintin
Wong, Alex CH
Spann, Benjamin C
Vincent, Jonathan N
Wong, Justin JL
Schlitzer, Andreas
Gorrell, Mark D
Weninger, Wolfgang
Roediger, Ben
Last Modified: 03 Jan 2021 22:32
URI: https://eprints.centenary.org.au/id/eprint/548

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