T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

被引：422

作者：

Arbore, Giuseppina ^{[1
]}

West, Erin E. ^{[2
]}

Spolski, Rosanne ^{[2
]}

Robertson, Avril A. B. ^{[3
]}

Klos, Andreas ^{[4
]}

Rheinheimer, Claudia ^{[4
]}

Dutow, Pavel ^{[4
]}

Woodruff, Trent M. ^{[3
]}

Yu, Zu Xi ^{[5
]}

O'Neill, Luke A. ^{[6
]}

Coll, Rebecca C. ^{[3
]}

Sher, Alan ^{[7
]}

Leonard, Warren J. ^{[2
]}

Koehl, Jorg ^{[8
,9
,10
]}

Monk, Pete ^{[11
]}

Cooper, Matthew A. ^{[3
]}

Arno, Matthew ^{[12
]}

Afzali, Behdad ^{[1
,13
]}

Lachmann, Helen J. ^{[14
]}

Cope, Andrew P. ^{[15
]}

Mayer-Barber, Katrin D. ^{[16
]}

Kemper, Claudia ^{[1
,2
]}

机构：

[1] Kings Coll London, Div Transplant Immunol & Mucosal Biol, MRC Ctr Transplantat, London SE1 9RT, England

[2] NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA

[3] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia

[4] Hannover Med Sch, Inst Med Microbiol & Hosp Epidemiol, D-30625 Hannover, Germany

[5] NHLBI, Pathol Core, Bldg 10, Bethesda, MD 20892 USA

[6] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland

[7] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA

[8] Med Univ Lubeck, Inst Syst Inflammat Res, D-23538 Lubeck, Germany

[9] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA

[10] Univ Cincinnati, Coll Med, Cincinnati, OH USA

[11] Univ Sheffield, Dept Infect & Immun, Sheffield S10 2RX, S Yorkshire, England

[12] Kings Coll London, Fac Life Sci & Med, Genom Ctr, London SE1 9NH, England

[13] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA

[14] UCL, Div Med, UK Natl Amyloidosis Ctr, Royal Free Campus, London NW3 2PF, England

[15] Kings Coll London, Div Immunol Infect & Inflammatory Dis, Acad Dept Rheumatol, London SE1 1UL, England

[16] NIAID, Lab Clin Infect Dis, Inflammat & Innate Immun Unit, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

SCIENCE | 2016年 / 352卷 / 6292期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

INNATE LYMPHOID-CELLS; C5A RECEPTOR CD88; INTESTINAL INFLAMMATION; IFN-GAMMA; DIFFERENTIATION; ACTIVATION; C5L2; CYTOKINE; DISEASE; ANTAGONISTS;

D O I：

10.1126/science.aad1210

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4+ Tcells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-g production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in Tcells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to innate immune cells" but is an integral component of normal adaptive TH1 responses."

引用

页数：5

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