NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release

Maurizio Vacca, Julia Böhme, Lia Paola Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W.S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro de Libero, Amit Singhal, Alessandra Mortellaro

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number1462
JournalFrontiers in Immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 2 2017

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Interleukin-12
Dendritic Cells
T-Lymphocytes
Mycobacterium tuberculosis
Toll-Like Receptor 9
Pattern Recognition Receptors
CD4 Antigens
Th1 Cells
Mycobacterium Infections
Ligation
Nucleotides
Growth

Keywords

  • CpG DNA
  • Dendritic cells
  • IFNγ
  • IL-12
  • Mycobacterium tuberculosis
  • NLRP10
  • T helper 1
  • Toll-like receptor 9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Vacca, M., Böhme, J., Zambetti, L. P., Khameneh, H. J., Paleja, B. S., Laudisi, F., ... Mortellaro, A. (2017). NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release. Frontiers in Immunology, 8(NOV), [1462]. https://doi.org/10.3389/fimmu.2017.01462

NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release. / Vacca, Maurizio; Böhme, Julia; Zambetti, Lia Paola; Khameneh, Hanif Javanmard; Paleja, Bhairav S.; Laudisi, Federica; Ho, Adrian W.S.; Neo, Kurt; Leong, Keith Weng Kit; Marzuki, Mardiana; Lee, Bernett; Poidinger, Michael; Santambrogio, Laura; Tsenova, Liana; Zolezzi, Francesca; de Libero, Gennaro; Singhal, Amit; Mortellaro, Alessandra.

In: Frontiers in Immunology, Vol. 8, No. NOV, 1462, 02.11.2017.

Research output: Contribution to journalArticle

Vacca, M, Böhme, J, Zambetti, LP, Khameneh, HJ, Paleja, BS, Laudisi, F, Ho, AWS, Neo, K, Leong, KWK, Marzuki, M, Lee, B, Poidinger, M, Santambrogio, L, Tsenova, L, Zolezzi, F, de Libero, G, Singhal, A & Mortellaro, A 2017, 'NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release', Frontiers in Immunology, vol. 8, no. NOV, 1462. https://doi.org/10.3389/fimmu.2017.01462
Vacca, Maurizio ; Böhme, Julia ; Zambetti, Lia Paola ; Khameneh, Hanif Javanmard ; Paleja, Bhairav S. ; Laudisi, Federica ; Ho, Adrian W.S. ; Neo, Kurt ; Leong, Keith Weng Kit ; Marzuki, Mardiana ; Lee, Bernett ; Poidinger, Michael ; Santambrogio, Laura ; Tsenova, Liana ; Zolezzi, Francesca ; de Libero, Gennaro ; Singhal, Amit ; Mortellaro, Alessandra. / NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release. In: Frontiers in Immunology. 2017 ; Vol. 8, No. NOV.
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