NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Hu, S; Du, X; Huang, Y; Fu, Y; Yang, Y; Zhan, X; He, W; Wen, Q; Zhou, X; Zhou, C; Zhong, X-P; Yang, J; Xiong, W; Wang, R; Gao, Y; Ma, L
Published Date
- August 2018
Published In
Volume / Issue
- 14 / 8
Start / End Page
- e1007266 -
PubMed ID
- 30133544
Pubmed Central ID
- 30133544
Electronic International Standard Serial Number (EISSN)
- 1553-7374
Digital Object Identifier (DOI)
- 10.1371/journal.ppat.1007266
Language
- eng
Conference Location
- United States