Details

Autor(en) / Beteiligte

• Sumpter, Tina L
• Thomson, Angus W

Titel

DAP12 renders liver dendritic cells resistant to maturation (91.14)

Ist Teil von

• The Journal of immunology (1950), 2009-04, Vol.182 (1_Supplement), p.91-91.14

Erscheinungsjahr

2009

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract Liver APC are constitutively exposed to gut-derived LPS, yet are refractory to LPS-induced maturation. We and others have hypothesized that resistance to LPS in liver DC reflects molecular inhibition of NF-κB activation. DNAX-activating protein of 12kDa (DAP12), a transmembrane adaptor protein, dampens co-stimulatory molecule and cytokine expression associated with inhibition of NF-κB in myeloid (m)DC. In this study, we evaluated the function of DAP12 in mDC (CD11c+CD11b+NK1.1-B220-) purified from livers or spleens of Fms-like tyrosine kinase 3 ligand (10 μg/day/10d)-mobilized C57BL/10 mice (in which DC populations were enriched), then cultured overnight with LPS. To test the hypothesis that DAP12 impairs LPS-induced maturation of liver mDC, DAP12 was silenced with siRNA (400nM) 2h prior to LPS stimulation. Liver mDC did not upregulate CD80, CD86, B7-H1 (PD-L1), B7RP or IL-12 to the extent of splenic mDC in response to LPS. Silencing DAP12 enhanced expression of CD80, CD86, IL-12 and the Th1-polarizing molecule, Delta4, but not B7-H1 or B7RP in liver and spleen mDC in response to LPS. These effects were more pronounced in liver mDC. We conclude that the comparatively immature state of liver mDC may be regulated, in part, by DAP12. Supported by American Liver Foundation and American Transplantation Society Fellowships and NIH RO1AI60994.