FcγRIIIa Signaling Modulates Endosomal TLR Responses in Human CD4⁺ T Cells.

ABSTRACT: Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). We show that in CD4⁺ T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid. Hydroxychloroquine used for treating systemic lupus erythematosus and a Syk inhibitor blocked NA-TLR localization with FcγRIIIa. Engaging TLR9 with CpG oligonucleotide contributes to the develo

SUBMITTER: Chauhan AK 

PROVIDER: S-EPMC5505339 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature