Distribution and kinetics of SR-PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells

Abstract

Dendritic cells (DCs) coordinate T cell responses by producing T cell-attracting chemokines and by inducing the expression of chemokine receptors on T cells. Scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) is a unique chemokine that also functions as an endocytic receptor and an adhesion molecule in its membrane-bound form. SR-PSOX/CXCL16 is the only known ligand of CXC chemokine receptor 6 (CXCR6) that is expressed on activated T cells and thus, may play an important role in enhancing effector functions of T cells. Here, we investigated the expression of SR-PSOX/CXCL16 on human DC subsets and that of CXCR6 on T cell subpopulations to elucidate the dynamics of CXCL16/CXCR6 interaction in DC/T cell responses. Membrane-bound SR-PSOX/CXCL16 was expressed on macrophages, monocyte-derived DCs, and blood myeloid DCs, and the expression increased after DC maturation. Myeloid antigen-presenting cells constitutively secreted SR-PSOX/CXCL16 for an extended period, suggesting the involvement of CXCL16 in peripheral and lymphoid tissues. Plasmacytoid DCs hardly expressed SR-PSOX/CXCL16 on their surfaces but secreted significant amounts of SR-PSOX/CXCL16. A subset of CD4+ effector memory T (T(EM)) cells constitutively expressed CXCR6, whereas central memory T cells (T(CM)) and naive T cells did not. Upon stimulation with mature DCs, however, the expression of CXCR6 on T(CM) cells was markedly up-regulated, whereas the expression on naive T cells was induced only weakly. These results suggest that the interaction between SR-PSOX/CXCL16 and CXCR6 plays an important role in enhancing T(CM) cell responses by mature DCs in lymphoid tissues and in augmenting T(EM) cell responses by macrophages in peripheral inflamed tissues.

CXCR6 identifies a putative population of retained human lung T cells characterised by co-expression of activation markers

“…CXCL16 has also been shown to be expressed by dendritic cells. (Tabata et al, 2005). We therefore hypothesise that CXCR6 positive cells recruited into the lung, become attracted to AM and to other APCs expressing CXCL16.…”

CXCL16 Influences the Nature and Specificity of CpG-Induced Immune Activation

“…CXCL16 is a scavenger receptor when expressed on the surface of pDCs and acts as a chemokine when proteolytically cleaved and released into the circulation (21)(22)(23)(24)(25)(26)(27). Based on the finding that SR ligands block the recognition of D ODN, we examined whether CXCL16 played a role in D ODN uptake.…”

CXCL16 in Vascular Pathology Research: from Macro Effects to microRNAs

“…Human monocytederived macrophages express CXCL16 on activation and in atherosclerotic lesions 10,[23][24][25] . CXCL16 expression at the mRNA level was also confirmed in B-cells 8) , 1) C-X-C motif chemokine domain with N-terminal signal sequence, 2) Mucin stalk, 3) Hydrophobic transmembrane domain, 4) Cytoplasmic tail with YXPV motif platelets 43) .…”

“…They include C, CC, CXC, and CX3C, where X represents an amino acid residue other than cysteine 6,7) . CXCL16 is a multi-domain chemokine that exists in the transmembrane and in a soluble dendritic cells 11,25) , smooth muscle cells 18,26,27) , T-cells 28) , and endothelial cells 3,18,26) . Studies that investigated the regulation of CXCL16 gene expression by proinflammatory stimuli in endothelial smooth muscle cells, human mononuclear cells, and atherosclerotic lesions of ApoE / mice have shown that the expression of CXCL16 mRNA is induced by INF and TNF , either separately or synergistically 8,18,24,27,29) .…”