Complement regulates conventional DC-mediated NK-cell activation by inducing TGF-β1 in Gr-1+ myeloid cells.

ABSTRACT: Complement activation modulates DC-mediated T-cell activation, but whether complement affects DC-mediated priming of NK cells is unknown. Here, we demonstrated that conventional DCs (cDCs) from C3(-/-) and C5aR(-/-) mice are hyperresponsive to polyI:C, a TLR3 ligand, leading to enhanced NK-cell activation. We found that cDCs lack C5a receptor (C5aR) and do not respond to C5a directly. Depletion of Gr-1(+) myeloid cells augments polyI:C-induced cDC activation in WT but not in C3(-/-) or C5aR(-/-) mice, indicating that the effect of complement activation on cDCs is indirectly mediated through C5aR-expressing Gr-1(+) myeloid cells. We further demonstrated that the mechanism by which Gr-1(+) myeloid cells regulate the activity of cDCs involves C5a-dependent TGF-β1 production in Gr-1(+)

SUBMITTER: Qing X 

PROVIDER: S-EPMC3653187 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature