1. NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.
- Author
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Hu, Shengfeng, Du, Xialin, Huang, Yulan, Fu, Yuling, Yang, Yalong, Zhan, Xiaoxia, He, Wenting, Wen, Qian, Zhou, Xinying, Zhou, Chaoying, Zhong, Xiao-Ping, Yang, Jiahui, Xiong, Wenjing, Wang, Ruining, Gao, Yuchi, and Ma, Li
- Subjects
T cells ,BACTERIAL diseases ,MYCOBACTERIUM tuberculosis ,CELL proliferation ,IMMUNITY ,CYTOKINES - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2018
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