Journal
CLINICAL IMMUNOLOGY
Volume 142, Issue 3, Pages 373-382Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2011.12.009
Keywords
Btk; TLRs; IFN-gamma; Antigen presenting cells; Natural killer cells
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Funding
- Health Research Board, Ireland [RP/2004/79, RP/2006/121]
- Science Foundation Ireland [08/IN.1/B2091]
- National Biophotonics and Imaging Platform Ireland
- Irish Government
- European Union
- Science Foundation Ireland (SFI) [08/IN.1/B2091] Funding Source: Science Foundation Ireland (SFI)
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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-gamma 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-gamma. Co-culture experiments demonstrate that Btk-deficient DCs were unable to drive wild-type or Btk-deficient NK cells to induce IFN-gamma 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. (C) 2011 Elsevier Inc. All rights reserved.
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