tetano
Editor, Senior Moderator
J Leukoc Biol. 2015 May 27. pii: jlb.3A0914-432RR. [Epub ahead of print]
[h=1]Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection.[/h] DeBerge MP[SUP]1[/SUP], Ely KH[SUP]2[/SUP], Wright PF[SUP]2[/SUP], Thorp EB[SUP]2[/SUP], Enelow RI[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Elevated levels of solTNFR2 are observed in a variety of human pathophysiological conditions but regulation of TNFR2 levels during disease is not well understood. We found that solTNFR2 levels were increased following influenza infection or live-attenuated influenza virus challenge in mice and humans, respectively. As influenza-specific CD8[SUP]+[/SUP] T cells up-regulated expression of TNFR2 after infection in mice, we hypothesized that CD8[SUP]+[/SUP] T cells contributed, in part, to solTNFR2 production after influenza infection and were interested in the mechanisms by which CD8[SUP]+[/SUP] T cells regulate TNFR2 shedding. Activation of these cells by TCR stimulation resulted in enhanced shedding of TNFR2 that required actin remodeling and lipid raft formation and was dependent on MAPK/ERK signaling. Furthermore, we identified ADAM17 as the protease responsible for TNFR2 shedding by CD8[SUP]+[/SUP] T cells, with ADAM17 and TNFR2 required in "cis" for shedding to occur. We observed similar activation thresholds for TNF-α expression and TNFR2 shedding, suggesting that solTNFR2 functioned, in part, to regulate solTNF-α levels. Production of solTNFR2 by activated CD8[SUP]+[/SUP] T cells reduced the availability of solTNF-α released by these cells, and TNFR2 blockade during influenza infection in mice enhanced the levels of solTNF-α, supporting this hypothesis. Taken together, this study identifies critical cellular mechanisms regulating TNFR2 shedding on CD8[SUP]+[/SUP] T cells and demonstrates that TNFR2 contributes, in part, to the regulation of TNF-α levels during infection.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] adaptive immunity; cytokine regulation; host response; viruses
PMID: 26019295 [PubMed - as supplied by publisher]
[h=1]Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection.[/h] DeBerge MP[SUP]1[/SUP], Ely KH[SUP]2[/SUP], Wright PF[SUP]2[/SUP], Thorp EB[SUP]2[/SUP], Enelow RI[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Elevated levels of solTNFR2 are observed in a variety of human pathophysiological conditions but regulation of TNFR2 levels during disease is not well understood. We found that solTNFR2 levels were increased following influenza infection or live-attenuated influenza virus challenge in mice and humans, respectively. As influenza-specific CD8[SUP]+[/SUP] T cells up-regulated expression of TNFR2 after infection in mice, we hypothesized that CD8[SUP]+[/SUP] T cells contributed, in part, to solTNFR2 production after influenza infection and were interested in the mechanisms by which CD8[SUP]+[/SUP] T cells regulate TNFR2 shedding. Activation of these cells by TCR stimulation resulted in enhanced shedding of TNFR2 that required actin remodeling and lipid raft formation and was dependent on MAPK/ERK signaling. Furthermore, we identified ADAM17 as the protease responsible for TNFR2 shedding by CD8[SUP]+[/SUP] T cells, with ADAM17 and TNFR2 required in "cis" for shedding to occur. We observed similar activation thresholds for TNF-α expression and TNFR2 shedding, suggesting that solTNFR2 functioned, in part, to regulate solTNF-α levels. Production of solTNFR2 by activated CD8[SUP]+[/SUP] T cells reduced the availability of solTNF-α released by these cells, and TNFR2 blockade during influenza infection in mice enhanced the levels of solTNF-α, supporting this hypothesis. Taken together, this study identifies critical cellular mechanisms regulating TNFR2 shedding on CD8[SUP]+[/SUP] T cells and demonstrates that TNFR2 contributes, in part, to the regulation of TNF-α levels during infection.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] adaptive immunity; cytokine regulation; host response; viruses
PMID: 26019295 [PubMed - as supplied by publisher]