气候变化领域集成服务门户(CCPortal): Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration

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DOI	10.1073/pnas.2025763118
	Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration
	Bastow C.R.; Bunting M.D.; Kara E.E.; McKenzie D.R.; Caon A.; Devi S.; Tolley L.; Mueller S.N.; Frazer I.H.; Harvey N.; Condina M.R.; Young C.; Hoffmann P.; McColl S.R.; Comerford I.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Leukocyte homing driven by the chemokine CCL21 is pivotal for adaptive immunity because it controls dendritic cell (DC) and T cell migration through CCR7. ACKR4 scavenges CCL21 and has been shown to play an essential role in DC trafficking at the steady state and during immune responses to tumors and cutaneous inflammation. However, the mechanism by which ACKR4 regulates peripheral DC migration is unknown, and the extent to which it regulates CCL21 in steady-state skin and lymph nodes (LNs) is contested. Specifically, our previous findings that CCL21 levels are increased in LNs of ACKR4-deficient mice [I. Comerford et al., Blood 116, 4130–4140 (2010)] were refuted [M. H. Ulvmar et al., Nat. Immunol. 15, 623–630 (2014)], and no differences in CCL21 levels in steady-state skin of ACKR4-deficient mice were reported despite compromised CCR7-dependent DC egress in these animals [S. A. Bryce et al., J. Immunol. 196, 3341–3353 (2016)]. Here, we resolve these issues and reveal that two forms of CCL21, full-length immobilized and cleaved soluble CCL21, exist in steady-state barrier tissues, and both are regulated by ACKR4. Without ACKR4, extracellular CCL21 gradients in barrier sites are saturated and nonfunctional, DCs cannot home directly to lymphatic vessels, and excess soluble CCL21 from peripheral tissues pollutes downstream LNs. The results identify the mechanism by which ACKR4 controls DC migration in barrier tissues and reveal a complex mode of CCL21 regulation in vivo, which enhances understanding of functional chemokine gradient formation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atypical chemokine receptors; Chemokines; Dendritic cells; Migration
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179718
作者单位	Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Science, The University of Adelaide, Adelaide, SA 5005, Australia; Genome Editing Laboratory, School of Medicine, The University of Adelaide, Adelaide, SA 5000, Australia; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia; The University of Queensland, Diamantina Institute, Translational Research Institute, Woolloongabba, QLD 4102, Australia; Centre for Cancer Biology, University of South Australia, SA Pathology, Adelaide, SA 5000, Australia; Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia
推荐引用方式 GB/T 7714	Bastow C.R.,Bunting M.D.,Kara E.E.,et al. Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration[J],2021,118(17).
APA	Bastow C.R..,Bunting M.D..,Kara E.E..,McKenzie D.R..,Caon A..,...&Comerford I..(2021).Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Bastow C.R.,et al."Scavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).