@article{dd353ce072464c7e9011cddd4815da03,
title = "NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release",
abstract = "NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10-/- mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10-/- dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10-/- DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon Mycobacterium tuberculosis (Mtb) infection, Nlrp10-/- mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb.",
keywords = "CpG DNA, Dendritic cells, IFNγ, IL-12, Mycobacterium tuberculosis, NLRP10, T helper 1, Toll-like receptor 9",
author = "Maurizio Vacca and Julia B{\"o}hme and Zambetti, {Lia Paola} and Khameneh, {Hanif Javanmard} and Paleja, {Bhairav S.} and Federica Laudisi and Ho, {Adrian W.S.} and Kurt Neo and Leong, {Keith Weng Kit} and Mardiana Marzuki and Bernett Lee and Michael Poidinger and Laura Santambrogio and Liana Tsenova and Francesca Zolezzi and {de Libero}, Gennaro and Amit Singhal and Alessandra Mortellaro",
note = "Funding Information: We thank Olaf R{\"o}tzschke, Maria Curotto de Lafaille [Singapore Immunology Network (SIgN)], Stephan Gasser and Herbert Schwarz (National University of Singapore) for supervision of MV, and Lucia Mori for valuable advice. We thank the SIgN flow cytometry facility for their help with cell sorting and the SIgN Mutant Mouse Collection Core Facility for providing mice. We also thank Insight Editing London for critically reviewing the manuscript. This work was supported by SIgN core funds, A*STAR Graduate Academy (SINGA Program) fellowship to MV, and A*STAR JCO-CDA 15302FG151 and Singapore-India Joint grant 1518224018 to AS. Publisher Copyright: {\textcopyright} 2017 Vacca, B{\"o}hme, Zambetti, Khameneh, Paleja, Laudisi, Ho, Neo, Leong, Marzuki, Lee, Poidinger, Santambrogio, Tsenova, Zolezzi, De Libero, Singhal and Mortellaro.",
year = "2017",
month = nov,
day = "2",
doi = "10.3389/fimmu.2017.01462",
language = "English (US)",
volume = "8",
journal = "Frontiers in immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "NOV",
}
