NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.
NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.
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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
DOI：
10.1371/journal.ppat.1007266
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发表时间：
2018-08
期刊：
影响因子：
6.7
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Hu S;Du X;Huang Y;Fu Y;Yang Y;Zhan X;He W;Wen Q;Zhou X;Zhou C;Zhong XP;Yang J;Xiong W;Wang R;Gao Y;Ma L
NLRC 3是NLR家族的成员，已被报道为先天免疫细胞中炎症信号通路的负调节剂。然而，NLRC 3在感染性疾病中调节CD 4 + T细胞应答的直接作用尚未研究。在本研究中，我们表明NLRC 3通过抑制肺和脾脏中的CD 4 + T细胞表型（包括分化、激活和增殖）发挥内在作用。CD 4 + T细胞中NLRC 3缺陷增强了针对结核分枝杆菌感染的保护性免疫应答。最后，我们证明NLRC 3缺陷通过负性调节NF-κB和MEK-ERK信号通路促进CD 4 + T细胞的活化、增殖和细胞因子产生。这项研究揭示了NLRC 3作为获得性免疫应答的直接调节剂的关键作用及其在M.肺结核感染。我们的研究结果还表明，NLRC 3作为一个潜在的目标，对结核病的治疗干预。
NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis.
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影响因子：
11.1
作者：
Hu S;He W;Du X;Yang J;Wen Q;Zhong XP;Ma L
通讯作者：
Ma L
影响因子：
9.1
作者：
Mortaz, Esmaeil;Adcock, Ian M.;Tabarsi, Payam;Masjedi, Mohammad Reza;Mansouri, Davood;Velayati, Ali Akbar;Casanova, Jean-Laurent;Barnes, Peter J.
通讯作者：
Barnes, Peter J.
影响因子：
6.4
作者：
Roberts, Teri;Beyers, Nulda;Walzl, Gerhard
通讯作者：
Walzl, Gerhard
影响因子：
64.8
作者：
Kimmey JM;Huynh JP;Weiss LA;Park S;Kambal A;Debnath J;Virgin HW;Stallings CL
通讯作者：
Stallings CL
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