To activate T cells effectively, dendritic cells (DCs) must provide three separate signals, MHC-Ag, costimulatory molecules (such as CD80 and CD86), and proinflammatory cytokines (such as IL-12). These three signals are up-regulated in the presence of "danger signals" such as LPS or viral nucleic acids. Evidence suggests that DCs providing only the first two of these signals cannot successfully stimulate T cells. Apoptotic cells have been proposed to suppress DC immunogenicity through the ligation of apoptotic cell receptors. Complement receptor 3 (CR3) and CD36 have been suggested to be important in this process, although the mechanism by which this modulation occurs is still unclear. We demonstrate that ligation of CR3, but not CD36, directs DCs to increase surface MHC and costimulatory molecules, while suppressing inflammatory cytokine release. CR3 modulation of DCs does not require a type I IFN response, does not involve the specific regulation of the MyD88- or Toll/IL-1R domain-containing adaptor-inducing IFN-[beta]-dependent TLR signaling pathways, and occurs even in the absence of danger signals. The functional outcome of this process is poor Ag-specific stimulation of CD4 and CD8 T cells by CR3-ligated DCs both in naive response as well as upon subsequent challenge with normal DCs. We propose that CR3 provides a "nondanger" signal that suppresses the stimulatory capacity of DCs.
Behrens, E.M., Sriram, U., Shivers, D.K., Gallucci, M., Ma, Z., Finkel, T.H., et al. (2007). Complement Receptor 3 Ligation of Dendritic Cells Suppresses Their Stimulatory Capacity. JOURNAL OF IMMUNOLOGY, 178(10), 6268-6279.
|Citazione:||Behrens, E.M., Sriram, U., Shivers, D.K., Gallucci, M., Ma, Z., Finkel, T.H., et al. (2007). Complement Receptor 3 Ligation of Dendritic Cells Suppresses Their Stimulatory Capacity. JOURNAL OF IMMUNOLOGY, 178(10), 6268-6279.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Titolo:||Complement Receptor 3 Ligation of Dendritic Cells Suppresses Their Stimulatory Capacity|
|Autori:||Behrens, EM; Sriram, U; Shivers, DK; Gallucci, M; Ma, Z; Finkel, TH; Gallucci, S|
|Data di pubblicazione:||2007|
|Rivista:||JOURNAL OF IMMUNOLOGY|
|Appare nelle tipologie:||01 - Articolo su rivista|