树突状细胞中 NLRC3 的表达可减弱 CD4 T 细胞应答和自身免疫。
NLRC3 expression in dendritic cells attenuates CD4 T cell response and autoimmunity.
机构信息
Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
出版信息
EMBO J. 2019 Aug 15;38(16):e101397. doi: 10.15252/embj.2018101397. Epub 2019 Jul 10.
Abstract
NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4 T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders.
摘要
核苷酸结合寡聚化结构域样受体（NLR）家族 C 型卷曲受体域蛋白 3（NLRC3），作为 NLR 家族的细胞内成员，是先天和适应性免疫细胞中炎症信号通路的负调控因子。先前的研究表明，NLRC3 在树突状细胞（DCs）中表达。然而，NLRC3 在 DC 激活和免疫原性中的作用尚不清楚。在本研究中，我们发现 NLRC3 减弱了 DC 的抗原呈递功能，以及其激活和极化 CD4 T 细胞为 Th1 和 Th17 亚群的能力。NLRC3 的缺失促进了致病性 Th1 和 Th17 反应，并增强了实验性自身免疫性脑脊髓炎（EAE）的发展。NLRC3 通过 p38 信号通路负调控 DC 的抗原呈递功能。用 NLRC3 过表达的 DC 进行疫苗接种可减轻 EAE 的进展。我们的研究结果支持 NLRC3 可作为治疗多发性硬化症和其他自身免疫性疾病的适应性免疫反应的潜在靶点。
相似文献
1
NLRC3 expression in dendritic cells attenuates CD4 T cell response and autoimmunity.树突状细胞中 NLRC3 的表达可减弱 CD4 T 细胞应答和自身免疫。
EMBO J. 2019 Aug 15;38(16):e101397. doi: 10.15252/embj.2018101397. Epub 2019 Jul 10.
2
The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity.天然免疫传感器 NLRC3 作为变阻器，可精细调节感染和自身免疫中的 T 细胞反应。
Immunity. 2018 Dec 18;49(6):1049-1061.e6. doi: 10.1016/j.immuni.2018.10.008.
3
NLRC3 attenuates osteoclastogenesis by limiting TNFα Th17 cell response in osteoporosis.NLRC3通过限制骨质疏松症中TNFα Th17细胞反应来减弱破骨细胞生成。
J Mol Med (Berl). 2024 May;102(5):655-665. doi: 10.1007/s00109-024-02422-y. Epub 2024 Mar 4.
4
C-Reactive Protein Suppresses the Th17 Response Indirectly by Attenuating the Antigen Presentation Ability of Monocyte Derived Dendritic Cells in Experimental Autoimmune Encephalomyelitis.在实验性自身免疫性脑脊髓炎中，C反应蛋白通过减弱单核细胞衍生树突状细胞的抗原呈递能力间接抑制Th17反应。
Front Immunol. 2021 Mar 25;12:589200. doi: 10.3389/fimmu.2021.589200. eCollection 2021.
5
1,25-dihydroxyvitamin D -induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells.1,25-二羟基维生素D诱导的树突状细胞通过增加调节性淋巴细胞比例并减少1型和17型辅助性T细胞来抑制实验性自身免疫性脑脊髓炎。
Immunology. 2017 Nov;152(3):414-424. doi: 10.1111/imm.12776. Epub 2017 Jul 10.
6
IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis.白细胞介素-7/白细胞介素-7受体信号传导对实验性自身免疫性脑脊髓炎中效应性CD4 + T细胞亚群有不同影响。
J Immunol. 2015 Sep 1;195(5):1974-83. doi: 10.4049/jimmunol.1403135. Epub 2015 Jul 29.
7
Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.多巴胺能刺激髓系抗原呈递细胞减轻信号转导和转录激活因子 3 的激活，有利于实验性自身免疫性脑脊髓炎的发展。
Front Immunol. 2018 Mar 21;9:571. doi: 10.3389/fimmu.2018.00571. eCollection 2018.
8
Canonical wnt signaling in dendritic cells regulates Th1/Th17 responses and suppresses autoimmune neuroinflammation.树突状细胞中的经典Wnt信号传导调节Th1/Th17反应并抑制自身免疫性神经炎症。
J Immunol. 2015 Apr 1;194(7):3295-304. doi: 10.4049/jimmunol.1402691. Epub 2015 Feb 20.
9
NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.NLRC3 负向调节 CD4+T 细胞，并影响结核分枝杆菌感染期间的保护性免疫。
PLoS Pathog. 2018 Aug 22;14(8):e1007266. doi: 10.1371/journal.ppat.1007266. eCollection 2018 Aug.
10
Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses.氨来呫诺通过抑制树突状细胞成熟和重编程效应器和调节性 T 细胞反应来减轻实验性自身免疫性脑脊髓炎。
J Neuroinflammation. 2019 Mar 1;16(1):52. doi: 10.1186/s12974-019-1438-z.
引用本文的文献
1
Role of NLRC3 in modulating inflammatory responses in neonates.NLRC3在调节新生儿炎症反应中的作用。
BMC Pediatr. 2025 May 28;25(1):428. doi: 10.1186/s12887-025-05766-7.
2
Mechanism and Application Prospects of NLRC3 Regulating cGAS-STING Pathway in Lung Cancer Immunotherapy.NLRC3 调控肺癌免疫治疗中 cGAS-STING 通路的机制及应用前景。
Int J Med Sci. 2024 Oct 7;21(13):2613-2622. doi: 10.7150/ijms.102328. eCollection 2024.
3
RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1.RNF213 通过促进 FOXO1 的 K63 连接泛素化和核转位来促进调节性 T 细胞分化。
Nat Commun. 2024 Jul 16;15(1):5961. doi: 10.1038/s41467-024-50392-z.
4
Acacetin Attenuates Sepsis-induced Acute Lung Injury via NLRC3-NF-κB Pathway.刺槐素通过NLRC3-NF-κB信号通路减轻脓毒症诱导的急性肺损伤
Inflammation. 2025 Feb;48(1):75-88. doi: 10.1007/s10753-024-02040-3. Epub 2024 May 13.
5
NLRC3 attenuates osteoclastogenesis by limiting TNFα Th17 cell response in osteoporosis.NLRC3通过限制骨质疏松症中TNFα Th17细胞反应来减弱破骨细胞生成。
J Mol Med (Berl). 2024 May;102(5):655-665. doi: 10.1007/s00109-024-02422-y. Epub 2024 Mar 4.
6
cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis.cGLRs 与模式识别受体家族的“表亲”一起调节免疫稳态。
Int J Mol Sci. 2024 Feb 2;25(3):1828. doi: 10.3390/ijms25031828.
7
Nlrc3 signaling is indispensable for hematopoietic stem cell emergence via Notch signaling in vertebrates.Nlrc3 信号在脊椎动物中通过 Notch 信号对于造血干细胞的出现是不可或缺的。
Nat Commun. 2024 Jan 3;15(1):226. doi: 10.1038/s41467-023-44251-6.
8
CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation.CXCR1 通过增强树突状细胞依赖性炎症驱动 EAE 和 ARDS 的发病机制。
Cell Death Dis. 2023 Sep 14;14(9):608. doi: 10.1038/s41419-023-06126-y.
9
RNF157 attenuates CD4 T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation.RNF157 通过促进 HDAC1 的泛素化和降解来减弱 CD4 T 细胞介导的自身免疫反应。
Theranostics. 2023 Jun 19;13(11):3509-3523. doi: 10.7150/thno.86307. eCollection 2023.
10
Triptoquinone A and B exercise a therapeutic effect in systemic lupus erythematosus by regulating NLRC3.三尖杉醌 A 和 B 通过调节 NLRC3 在系统性红斑狼疮中发挥治疗作用。
PeerJ. 2023 Jun 9;11:e15395. doi: 10.7717/peerj.15395. eCollection 2023.
本文引用的文献
1
Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon.病毒 DNA 与 NLRC3（一种抑制性核酸传感器）结合，激活 STING（一种环状二核苷酸受体），从而激活 I 型干扰素。
Immunity. 2019 Mar 19;50(3):591-599.e6. doi: 10.1016/j.immuni.2019.02.009.
2
The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity.天然免疫传感器 NLRC3 作为变阻器，可精细调节感染和自身免疫中的 T 细胞反应。
Immunity. 2018 Dec 18;49(6):1049-1061.e6. doi: 10.1016/j.immuni.2018.10.008.
3
Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells.调控性 NLR 家族蛋白控制人类树突状细胞中 RLR 介导的 I 型干扰素和炎症反应。
Front Immunol. 2018 Oct 5;9:2314. doi: 10.3389/fimmu.2018.02314. eCollection 2018.
4
NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.NLRC3 负向调节 CD4+T 细胞，并影响结核分枝杆菌感染期间的保护性免疫。
PLoS Pathog. 2018 Aug 22;14(8):e1007266. doi: 10.1371/journal.ppat.1007266. eCollection 2018 Aug.
5
Unconventional T Cell Targets for Cancer Immunotherapy.非传统 T 细胞靶点在癌症免疫治疗中的应用
Immunity. 2018 Mar 20;48(3):453-473. doi: 10.1016/j.immuni.2018.03.009.
6
Innate immune receptors for cross-presentation: The expanding role of NLRs.天然免疫受体在交叉呈递中的作用：NLRs 的作用不断扩大。
Mol Immunol. 2019 Sep;113:6-10. doi: 10.1016/j.molimm.2017.11.028. Epub 2017 Nov 29.
7
NLRP10 Enhances CD4 T-Cell-Mediated IFNγ Response Regulation of Dendritic Cell-Derived IL-12 Release.NLRP10增强CD4 T细胞介导的IFNγ反应 对树突状细胞衍生的IL-12释放的调节。
Front Immunol. 2017 Nov 2;8:1462. doi: 10.3389/fimmu.2017.01462. eCollection 2017.
8
The Scaffolding Protein IQGAP1 Interacts with NLRC3 and Inhibits Type I IFN Production.支架蛋白IQGAP1与NLRC3相互作用并抑制I型干扰素的产生。
J Immunol. 2017 Oct 15;199(8):2896-2909. doi: 10.4049/jimmunol.1601370. Epub 2017 Sep 1.
9
IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.中性粒细胞产生的白介素-17 增强了抗细菌能力，但在结核分枝杆菌感染期间促进了关节炎的发展。
EBioMedicine. 2017 Sep;23:88-99. doi: 10.1016/j.ebiom.2017.08.001. Epub 2017 Aug 9.
10
NLRC3 promotes host resistance against Pseudomonas aeruginosa-induced keratitis by promoting the degradation of IRAK1.NLRC3通过促进IRAK1的降解来增强宿主对铜绿假单胞菌诱导的角膜炎的抵抗力。
Int J Mol Med. 2017 Sep;40(3):898-906. doi: 10.3892/ijmm.2017.3077. Epub 2017 Jul 20.
Zotero 插件