CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability

被引：71

作者：

Ivanov, Stoyan ^{[1
,8
]}

Scallan, Joshua P. ^{[2
,9
]}

Kim, Ki-Wook ^{[1
]}

Werth, Kathrin ^{[3
]}

Johnson, Michael W. ^{[1
,4
]}

Saunders, Brian T. ^{[1
]}

Wang, Peter L. ^{[1
]}

Kuan, Emma L. ^{[5
,10
]}

Straub, Adam C. ^{[6
,11
]}

Ouhachi, Melissa ^{[7
]}

Weinstein, Erica G. ^{[5
]}

Williams, Jesse W. ^{[1
]}

Briseno, Carlos ^{[1
]}

Colonna, Marco ^{[1
]}

Isakson, Brant E. ^{[6
]}

Gautier, Emmanuel L. ^{[1
,7
]}

Foerster, Reinhold ^{[3
]}

Davis, Michael J. ^{[2
]}

Zinselmeyer, Bernd H. ^{[1
]}

Randolph, Gwendalyn J. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, 425 S Euclid Ave,Box 8118, St Louis, MO 63110 USA

[2] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO USA

[3] Hannover Med Sch, Inst Immunol, Hannover, Germany

[4] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

[5] Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA

[6] Univ Virginia, Sch Med, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

[7] Univ Paris 06, INSERM, Sorbonne Univ, UMRS 1166,Pitie Salpetriere Hosp, Paris, France

[8] Univ Nice, Nice, France

[9] Univ S Florida, Tampa, FL USA

[10] Benaroya Res Inst, Immunol Program, Seattle, WA USA

[11] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2016年 / 126卷 / 04期

关键词：

IN-VIVO; IMMUNE-RESPONSE; NODES; DIFFERENTIATION; FLOW; MIGRATION; PRESSURE; FACTOR-4; CD103(+); ANTIGEN;

D O I：

10.1172/JCI84518

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7(-/-) mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4(+)) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4(fl/fl) mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs.

引用

页码：1581 / 1591

页数：11

共 42 条

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