Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity.
Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity.
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具有NLRP 3炎性体活化的Tfh细胞对于高亲和力抗体产生、生殖中心形成和自身免疫是必需的。
DOI：
10.1136/annrheumdis-2021-221985
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发表时间：
2022-07
影响因子：
27.4
通讯作者：
Fu, Shu Man
中科院分区：
文献类型：
--
作者：
Zhao, Zhenhuan;Xu, Bihua;Wang, Shuang;Zhou, Mianjing;Huang, Yuefang;Guo, Chaohuan;Li, Mengyuan;Zhao, Jijun;Sung, Sun-Sang J.;Gaskin, Felicia;Yang, Niansheng;Fu, Shu Man
NLRP 3炎性体调节T细胞应答。本研究检测了NLRP 3炎性小体激活在调节Tfh细胞对T依赖性抗原的体液应答和系统性红斑狼疮（SLE）中的作用。使用荧光标记的半胱天冬酶-1抑制剂探针，在B6、MRL/lpr和NZM 2328小鼠以及SLE患者和健康对照中研究了Tfh细胞的NLRP 3炎性体活化。用选择性NLRP 3抑制剂MCC 950研究NLRP 3炎性小体激活与生殖中心（GC）反应、免疫应答和自身抗体产生的关系。在B6小鼠中鉴定了免疫后Tfh细胞中的NLRP 3炎性体活化。MCC 950可抑制对sRBC和NP-CGG的体液反应，同时降低GC反应。淋巴细胞特异性缺失NLRP 3或Casp 1的B6小鼠产生了次优的体液应答，GC形成受损，亲和力成熟缺陷。在MRL/lpr和NZM 2328小鼠中，抑制NLRP 3活化抑制了NLRP 3活化的Tfh细胞扩增以及减弱的狼疮样表型。具有活化的NLRP 3炎性体的Tfh细胞表现出增加的Tfh细胞功能和分化分子的表达，并且具有更大的活化B细胞的能力。在SLE患者中，疾病活动性与活化的NLRP 3 + Tfh群体的增加呈正相关，并且该群体对治疗的反应显著降低。Tfh细胞中NLRP 3炎性体的活化是免疫应答的组成部分。活化的NLRP 3 + Tfh群体对于最佳体液应答、GC形成和自身免疫是必不可少的。
NLRP3 inflammasome regulates T cell responses. This study examined the roles of NLRP3 inflammasome activation in the regulation of Tfh cells during humoral response to T dependent antigens and in systemic lupus erythematosus (SLE). NLRP3 inflammasome activation of Tfh cells was studied in B6, MRL/lpr and NZM2328 mice and in SLE patients and healthy controls using a fluorescence-labeled caspase-1 inhibitor probe. MCC950, a selective inhibitor of NLRP3, was used to investigate the relation between NLRP3 inflammasome activation and germinal center (GC) reaction, Ab responses to immunization, and autoantibody production. NLRP3 inflammasome activation in Tfh cells after immunization was identified in B6 mice. MCC950 inhibited humoral responses to sRBC and NP-CGG with reduction of the GC reaction. B6 mice with lymphoid cell-specific deletion of NLRP3 or Casp1 mounted sub-optimal humoral responses with impaired GC formation and defective affinity maturation. In MRL/lpr and NZM2328 mice, inhibition of NLRP3 activation suppressed NLRP3 activated Tfh cell expansion as well as attenuated lupus-like phenotypes. Tfh cells with activated NLRP3 inflammasome exhibited increased expression of molecules for Tfh cell function and differentiation, and had greater ability to activate B cells. In SLE patients, disease activity was positively correlated with an increase in the activated NLRP3+ Tfh population and this population was markedly reduced in response to therapy. The activation of NLRP3 inflammasome in Tfh cells is an integral part of responses to immunization. The activated NLRP3+ Tfh population is essential for optimal humoral responses, GC formation and autoimmunity.
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影响因子：
13.3
作者：
Kahlenberg, J. Michelle;Yalavarthi, Srilakshmi;Zhao, Wenpu;Hodgin, Jeffrey B.;Reed, Tamra J.;Tsuji, Noriko M.;Kaplan, Mariana J.
通讯作者：
Kaplan, Mariana J.
DOI：
10.1073/pnas.0902745106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ben-Sasson, Shlomo Z.;Hu-Li, Jane;Paul, William E.
通讯作者：
Paul, William E.
影响因子：
5.6
作者：
Chen, Mingkuan;Wang, Hongbin;Meng, Guangxun
通讯作者：
Meng, Guangxun
T 辅助细胞 1 免疫需要 CD4⁺ T 细胞中补体驱动的 NLRP3 炎性体活性。
DOI：
10.1126/science.aad1210
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arbore G;West EE;Spolski R;Robertson AAB;Klos A;Rheinheimer C;Dutow P;Woodruff TM;Yu ZX;O'Neill LA;Coll RC;Sher A;Leonard WJ;Köhl J;Monk P;Cooper MA;Arno M;Afzali B;Lachmann HJ;Cope AP;Mayer-Barber KD;Kemper C
通讯作者：
Kemper C
DOI：
10.4049/jimmunol.181.9.6027
发表时间：
2008-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Le TV;Kim TH;Chaplin DD
通讯作者：
Chaplin DD