Immune complexes and late complement proteins trigger activation of Syk tyrosine kinase in human CD4+ T cells

Abstract

SummaryIn systemic lupus erythematosus (SLE), the autoantibodies that form immune complexes (

FcγRIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulates Toll-like Receptor (TLR) Expression

“…ϩ T-cells in the patient population is also supported by our previous studies where we showed Syk phosphorylation during T-cell activation (38). A role for Syk in the development of T H 1 and T H 17 responses via dendritic cell activation has been also been suggested (49).…”

“…ϩ T-cells that express Fc␥RIIIa, ICs ligation triggers FcR␥ chain phosphorylation, which then co-localizes and signal via Syk (38,53). Although C5b-9 is essential to trigger MR clustering, ICs engage Fc␥RIIIa and trigger Syk activation (11).…”

“…A small population of IFN-␥ high IL-17A ϩ was observed from co-stimulation by ICsϩC5b-9. (11,38,39). The nature of the ICs used has been characterized for their binding to Fc␥RIII in multiple cell types, compared with AHG and anti-Fc␥RIIIa antibody (clone 3G8) (40).…”

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

“…In CD4 ϩ T-cells, engagement of the FcRs by ICs led to the phosphorylation of FcR-␥ chain, which co-localized with phosphorylated Syk kinase (43). In the present study, we show activation induced expression of Fc␥RIIIa in a subset of activated CD4 ϩ T-cells that upon ligation from ICs led to the development of a cell phenotype that produced high amounts of IFN-␥ and expressed T-bet.…”

“…10). Increased IC binding was also observed directly in the CD4 ϩ population in SLE patients (43). The IC binding and staining with receptor specific antibodies demonstrated IC co-localization with the receptors (Fig.…”