Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-γ production by natural killer cells

Joan Ní Gabhann, Shaun Spence, Claire Wynne, Siobhán Smith, Jennifer C. Byrne, Barbara Coffey, Kevin Stacey, Adrien Kissenpfennig, Jim Johnston, Caroline A. Jefferies

Research output: Contribution to journalArticlepeer-review

Abstract

This study defines a critical role for Btk in regulating TLR4-induced crosstalk between antigen presenting cells (APCs) and natural killer (NK) cells. Reduced levels of IL-12, IL-18 and IFN-γ were observed in Btk-deficient mice and ex vivo generated macrophages and dendritic cells (DCs) following acute LPS administration, whilst enhanced IL-10 production was observed. In addition, upregulation of activation markers and antigen presentation molecules on APCs was also impaired in the absence of Btk. APCs, by virtue of their ability to produce IL-12 and IL-18, are strong inducers of NK-derived IFN-γ Co-culture experiments demonstrate that Btk-deficient DCs were unable to drive wild-type or Btk-deficient NK cells to induce IFN-γ production, whereas these responses could be restored by exogenous administration of IL-12 and IL-18. Thus Btk is a critical regulator of APC-induced NK cell activation by virtue of its ability to regulate IL-12 and IL-18 production in response to acute LPS administration.

Original languageEnglish
Pages (from-to)373-382
Number of pages10
JournalClinical Immunology
Volume142
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

Keywords

  • Antigen presenting cells
  • Btk
  • IFN-γ
  • Natural killer cells
  • TLRs

Fingerprint

Dive into the research topics of 'Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-γ production by natural killer cells'. Together they form a unique fingerprint.

Cite this