Innate IL-17A promotes Coxsackievirus B3-induced myocarditis by amplifying adaptive Th17 response: a role for Vγ4 γδT Cells
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- 英文论文题名：Innate IL-17A promotes Coxsackievirus B3-induced myocarditis by amplifying adaptive Th17 response: a role for Vγ4 γδT Cells
- 论文作者：Wei XU ; Fangfang Wan
- 英文论文作者：Wei XU ; Fangfang Wan ; Institutes of Biology and Medical Sciences ; Soochow University
- 年：2016
- 作者机构：Institutes of Biology and Medical Sciences,Soochow University;
- 英文论文关键词：myocarditis ; coxsackievirus ; IL-17 ; γδT
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R542.21
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：353k
- 原文格式：D
- 会议级别：全国
摘要
Objective: Coxsackievirus B3(CVB3) infection of the myocardium and the associated inflammatory response are important determinants of viral myocarditis(VMC). IL-17 A is one of critical effector cytokines responsible for CVB3-myocarditis. However, the respective role of IL-17A-producing γδT cells, as opposed to Th17 cells, has not been fully addressed. Methods: To investigate the importance of γδT-produced IL-17 A in the development of acute myocarditis, Viral myocarditis was induced into C57B6 mice by injection of 103 pfu of CVB3. IL-17 A level in the heart and the cellular source of IL-17 A was evaluated. The level of cardiac inflammation, viral titers and cytokine production were measured in mice deficient of IL-17 A, TCRγδ and Vγ4 γδT cells following CVB3 infection. Results: Infection of C57 mice with CVB3 induced a continued up-regulation of IL-17 A and an early infiltration of IL-17A-producing Vγ4+γδT cells in the inflamed heart, which accounted for 55% of the IL-17 producing cells on day 7 postinfection. Both IL-17 A or TCRδ deficient mice developed a decreased myocarditis verifying the detrimental role of IL-17 A and γδT cells in the acute phase of CVB3 infection. Anti-Vγ4+ treatment significantly reduced viral replication and protected mice from myocarditis. Transfer of IL-17 A KO-derived γδT cells into TCRδ KO recipient mice failed to enhance myocarditis as achieved by WT-derived γδT transfer indicating IL-17 A was critical pathogenic effector cytokine for Vγ4γδT to increase viral myocarditis. Early IL-1β and IL-23-activated γδ T cells promoted the proliferation and IL-17 production by CD8~+ T cells.Conclusions: Our findings demonstrate that Vγ4 γδT cells, appearing early in the heart of mice during acute CVB3 infection, have a pathogenic role in early IL-17 production which increases the susceptibility of mice to myocarditis by amplifying the quantity and function of local Th17 response.
Objective: Coxsackievirus B3(CVB3) infection of the myocardium and the associated inflammatory response are important determinants of viral myocarditis(VMC). IL-17 A is one of critical effector cytokines responsible for CVB3-myocarditis. However, the respective role of IL-17A-producing γδT cells, as opposed to Th17 cells, has not been fully addressed. Methods: To investigate the importance of γδT-produced IL-17 A in the development of acute myocarditis, Viral myocarditis was induced into C57B6 mice by injection of 10~3 pfu of CVB3. IL-17 A level in the heart and the cellular source of IL-17 A was evaluated. The level of cardiac inflammation, viral titers and cytokine production were measured in mice deficient of IL-17 A, TCRγδ and Vγ4 γδT cells following CVB3 infection. Results: Infection of C57 mice with CVB3 induced a continued up-regulation of IL-17 A and an early infiltration of IL-17A-producing Vγ4+γδT cells in the inflamed heart, which accounted for 55% of the IL-17 producing cells on day 7 postinfection. Both IL-17 A or TCRδ deficient mice developed a decreased myocarditis verifying the detrimental role of IL-17 A and γδT cells in the acute phase of CVB3 infection. Anti-Vγ4+ treatment significantly reduced viral replication and protected mice from myocarditis. Transfer of IL-17 A KO-derived γδT cells into TCRδ KO recipient mice failed to enhance myocarditis as achieved by WT-derived γδT transfer indicating IL-17 A was critical pathogenic effector cytokine for Vγ4γδT to increase viral myocarditis. Early IL-1β and IL-23-activated γδ T cells promoted the proliferation and IL-17 production by CD4+ T cells.Conclusions: Our findings demonstrate that Vγ4 γδT cells, appearing early in the heart of mice during acute CVB3 infection, have a pathogenic role in early IL-17 production which increases the susceptibility of mice to myocarditis by amplifying the quantity and function of local Th17 response.
Objective: Coxsackievirus B3(CVB3) infection of the myocardium and the associated inflammatory response are important determinants of viral myocarditis(VMC). IL-17 A is one of critical effector cytokines responsible for CVB3-myocarditis. However, the respective role of IL-17A-producing γδT cells, as opposed to Th17 cells, has not been fully addressed. Methods: To investigate the importance of γδT-produced IL-17 A in the development of acute myocarditis, Viral myocarditis was induced into C57B6 mice by injection of 10~3 pfu of CVB3. IL-17 A level in the heart and the cellular source of IL-17 A was evaluated. The level of cardiac inflammation, viral titers and cytokine production were measured in mice deficient of IL-17 A, TCRγδ and Vγ4 γδT cells following CVB3 infection. Results: Infection of C57 mice with CVB3 induced a continued up-regulation of IL-17 A and an early infiltration of IL-17A-producing Vγ4+γδT cells in the inflamed heart, which accounted for 55% of the IL-17 producing cells on day 7 postinfection. Both IL-17 A or TCRδ deficient mice developed a decreased myocarditis verifying the detrimental role of IL-17 A and γδT cells in the acute phase of CVB3 infection. Anti-Vγ4+ treatment significantly reduced viral replication and protected mice from myocarditis. Transfer of IL-17 A KO-derived γδT cells into TCRδ KO recipient mice failed to enhance myocarditis as achieved by WT-derived γδT transfer indicating IL-17 A was critical pathogenic effector cytokine for Vγ4γδT to increase viral myocarditis. Early IL-1β and IL-23-activated γδ T cells promoted the proliferation and IL-17 production by CD4+ T cells.Conclusions: Our findings demonstrate that Vγ4 γδT cells, appearing early in the heart of mice during acute CVB3 infection, have a pathogenic role in early IL-17 production which increases the susceptibility of mice to myocarditis by amplifying the quantity and function of local Th17 response.
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