RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity

被引：50

作者：

Chopin, Michael ^{[1
,2
]}

Preston, Simon P. ^{[1
,2
]}

Lun, Aaron T. L. ^{[1
,2
]}

Tellier, Julie ^{[1
,2
]}

Smyth, Gordon K. ^{[1
,3
]}

Pellegrini, Marc ^{[1
,2
]}

Belz, Gabrielle T. ^{[1
,2
]}

Corcoran, Lynn M. ^{[1
,2
]}

Visvader, Jane E. ^{[1
,2
]}

Wu, Li ^{[1
,2
,4
]}

Nutt, Stephen L. ^{[1
,2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, 1G Royal Parade, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[3] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia

[4] Tsinghua Univ, Inst Immunol, Sch Med, Beijing 100084, Peoples R China

来源：

CELL REPORTS | 2016年 / 15卷 / 04期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

TRANSCRIPTION FACTOR E2-2; I INTERFERON; CLEIDOCRANIAL DYSPLASIA; CHORIOMENINGITIS VIRUS; CXCR4; ANTAGONIST; PROGENITOR CELLS; GENE-EXPRESSION; HUMAN BLOOD; DIFFERENTIATION; CHEMOKINES;

D O I：

10.1016/j.celrep.2016.03.066

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Plasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-alpha expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.

引用

页码：866 / 878

页数：13

共 47 条

[1] Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses [J].