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	Frontline science: nasal epithelial gm-csf contributes to tlr5-mediated modulation of airway dendritic cells and subsequent iga response
	Cao, Yuan; Zhang, Ejuan; Yang, Jingyi; Yang, Yi; Yu, Jie; Xiao, Yang; Li, Wei; Zhou, Dihan; Li, Yaoming; Zhao, Bali
刊名	Journal of leukocyte biology
	2017-09-01
卷号	102期号:3页码:575-587
关键词	Innate immunity Adaptive immunity Cell activation Adjuvant
ISSN号	0741-5400
DOI	10.1189/jlb.3hi0816-368rr
通讯作者	Zhong, maohua(zmh@wh.iov.cn) ; Yan, huimin(hmyan@wh.iov.cn)
英文摘要	Flagellin, as a tlr5 agonist, is an established mucosal adjuvant for enhancing mucosal iga responses by i.n. immunization. nasal epithelial cells (necs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. however, the molecular mechanism leading to modulation and the response by flagellin-activated necs remain unknown. we aimed to identify the soluble mediator(s) from flagellin-activated necs that modulate the functions of airway dendritic cells (dcs) and enhance subsequent iga response. in vitro studies showed that compared with the tlr4 agonist lps, flagellin directly triggered slight up-regulation of cd80 on airway dcs but was insufficient to affect cd86 expression and dc-mediated iga response. with the use of an in vitro system for culturing mouse primary necs (mnecs), we demonstrated that flagellin-activated mnecs could functionally modulate airway dcs, which manifested as significant up-regulation of cd80/cd86 and enhancement of iga production. the functional modulation of airway dcs was dependent on tlr5 activation of mnecs rather than direct tlr5 activation of airway dcs. with the use of cytokine array and antibody-blocking assays, we further identified that gm-csf, a cytokine secreted from tlr5-activated mnecs, contributes to the activation of mnecs to airway dcs and subsequent iga enhancement. in vivo blocking experiments confirmed that gm-csf is an important factor in recombinant flagellin derived from salmonella typhi (flic)-induced airway dc activation and antigen-specific iga enhancement. our data directly demonstrate that nasal epithelial gm-csf contributes to tlr5-mediated modulation of airway dcs and a subsequent iga response.
WOS关键词	COLONY-STIMULATING FACTOR ; MUCOSAL ADJUVANT ACTIVITY ; INFLUENZA VACCINE ; HUMORAL IMMUNITY ; INDUCE IGA ; FLAGELLIN ; RECEPTOR ; EXPRESSION ; PROMOTES ; AGONIST
WOS研究方向	Cell Biology ; Hematology ; Immunology
WOS类目	Cell Biology ; Hematology ; Immunology
语种	英语
出版者	FEDERATION AMER SOC EXP BIOL
WOS记录号	WOS:000413395700005
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373401
专题	武汉病毒研究所
通讯作者	Zhong, Maohua; Yan, Huimin
作者单位	Chinese Acad Sci, Wuhan Inst Virol, Mucosal Immun Res Grp, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Cao, Yuan,Zhang, Ejuan,Yang, Jingyi,et al. Frontline science: nasal epithelial gm-csf contributes to tlr5-mediated modulation of airway dendritic cells and subsequent iga response[J]. Journal of leukocyte biology,2017,102(3):575-587.
APA	Cao, Yuan.,Zhang, Ejuan.,Yang, Jingyi.,Yang, Yi.,Yu, Jie.,...&Yan, Huimin.(2017).Frontline science: nasal epithelial gm-csf contributes to tlr5-mediated modulation of airway dendritic cells and subsequent iga response.Journal of leukocyte biology,102(3),575-587.
MLA	Cao, Yuan,et al."Frontline science: nasal epithelial gm-csf contributes to tlr5-mediated modulation of airway dendritic cells and subsequent iga response".Journal of leukocyte biology 102.3(2017):575-587.

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