IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities.
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IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities. / Orinska, Zane; Maurer, Marcus; Mirghomizadeh, Farhad; Bulanova, Elena; Metz, Martin; Nashkevich, Natalia; Schiemann, Florian; Schulmistrat, Jan; Budagian, Vadim; Giron-Michel, Julien; Brandt, Ernst; Paus, Ralf; Bulfone-Paus, Silvia.
In: NAT MED, Vol. 13, No. 8, 8, 2007, p. 927-934.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities.
AU - Orinska, Zane
AU - Maurer, Marcus
AU - Mirghomizadeh, Farhad
AU - Bulanova, Elena
AU - Metz, Martin
AU - Nashkevich, Natalia
AU - Schiemann, Florian
AU - Schulmistrat, Jan
AU - Budagian, Vadim
AU - Giron-Michel, Julien
AU - Brandt, Ernst
AU - Paus, Ralf
AU - Bulfone-Paus, Silvia
PY - 2007
Y1 - 2007
N2 - Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly. Deletion of Il15 in mice markedly increases chymase activities, leading to greater MC bactericidal responses, increased processing and activation of neutrophil-recruiting chemokines, and significantly higher survival rates of mice after septic peritonitis. By showing that intracellular IL-15 acts as a specific negative transcriptional regulator of a mouse MC chymase (mast cell protease-2), we provide evidence that defined MC protease activity is transcriptionally regulated by an intracellularly retained cytokine. Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis.
AB - Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly. Deletion of Il15 in mice markedly increases chymase activities, leading to greater MC bactericidal responses, increased processing and activation of neutrophil-recruiting chemokines, and significantly higher survival rates of mice after septic peritonitis. By showing that intracellular IL-15 acts as a specific negative transcriptional regulator of a mouse MC chymase (mast cell protease-2), we provide evidence that defined MC protease activity is transcriptionally regulated by an intracellularly retained cytokine. Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis.
M3 - SCORING: Zeitschriftenaufsatz
VL - 13
SP - 927
EP - 934
JO - NAT MED
JF - NAT MED
SN - 1078-8956
IS - 8
M1 - 8
ER -