NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.

Published

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 22, 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

International Standard Serial Number (ISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1007266

Language

  • eng