TY - JOUR
T1 - Ig-like transcript 7, but not bone marrow stromal cell antigen 2 (Also Known as HM1.24, Tetherin, or CD317) modulates plasmacytoid dendritic cell function in primary human blood leukocytes
AU - Tavano, Barbara
AU - Galao, Rui Pedro
AU - Graham, David R.
AU - Neil, Stuart J.D.
AU - Aquino, Veronica N.
AU - Fuchs, Dietmar
AU - Boasso, Adriano
PY - 2013/3/15
Y1 - 2013/3/15
N2 - The Ig-like transcript (ILT) 7 is a surface molecule selectively expressed by human plasmacytoid dendritic cells (pDCs). ILT7 crosslinking suppresses pDC activation and type I IFN (IFN-I) secretion following TLR7/9 engagement. The bone marrow stromal cell Ag 2 (BST2, aka HM1.24, tetherin, or CD317) is expressed by different cell types upon exposure to IFN-I and is a natural ligand for ILT7. In this study, we show that ILT7 expression decreased spontaneously in pDCs upon in vitro culture, which correlates with pDC differentiation measured as increased side scatter properties and CCR7 expression. TLR7/9 ligands, as well as HIV, induced BST2 upregulation on all tested cell types except T cells, which required TCR stimulation to respond to TLR9L-induced IFN-I. IFN-γ, IL- 4, IL-10, and TNF-α had only marginal effects on BST2 expression in blood leukocytes compared with TLR9L. Preincubation with ILT7 cross-linking Ab inhibited IFN-I production in PBMCs treated with TLR7/9L or HIV, whereas BST2 blockade did not affect IFN-I responses even when BST2 upregulation was further boosted with TCR agonists or immunoregulatory cytokines. Our data indicate that BST2-mediated ILT7 cross-linking may act as a homeostatic regulatory mechanism on immature circulating pDC, rather than a negative feedback for activated mature pDCs that have downregulated ILT7.
AB - The Ig-like transcript (ILT) 7 is a surface molecule selectively expressed by human plasmacytoid dendritic cells (pDCs). ILT7 crosslinking suppresses pDC activation and type I IFN (IFN-I) secretion following TLR7/9 engagement. The bone marrow stromal cell Ag 2 (BST2, aka HM1.24, tetherin, or CD317) is expressed by different cell types upon exposure to IFN-I and is a natural ligand for ILT7. In this study, we show that ILT7 expression decreased spontaneously in pDCs upon in vitro culture, which correlates with pDC differentiation measured as increased side scatter properties and CCR7 expression. TLR7/9 ligands, as well as HIV, induced BST2 upregulation on all tested cell types except T cells, which required TCR stimulation to respond to TLR9L-induced IFN-I. IFN-γ, IL- 4, IL-10, and TNF-α had only marginal effects on BST2 expression in blood leukocytes compared with TLR9L. Preincubation with ILT7 cross-linking Ab inhibited IFN-I production in PBMCs treated with TLR7/9L or HIV, whereas BST2 blockade did not affect IFN-I responses even when BST2 upregulation was further boosted with TCR agonists or immunoregulatory cytokines. Our data indicate that BST2-mediated ILT7 cross-linking may act as a homeostatic regulatory mechanism on immature circulating pDC, rather than a negative feedback for activated mature pDCs that have downregulated ILT7.
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U2 - 10.4049/jimmunol.1202391
DO - 10.4049/jimmunol.1202391
M3 - Article
C2 - 23401591
AN - SCOPUS:84874823706
SN - 0022-1767
VL - 190
SP - 2622
EP - 2630
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -