Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells
Resheq YJ, Li KK, Ward ST, Wilhelm A, Garg A, Curbishley SM, Blahova M, Zimmermann HW, Jitschin R, Mougiakakos D, Mackensen A, Weston CJ, Adams DH (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 194
Pages Range: 2578-86
Journal Issue: 6
Abstract
Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14(+) monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = -0.6555, p < 0.05). Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy.
Authors with CRIS profile
Dimitrios Mougiakakos
Professur für CAR-T-Zell-Therapie
Andreas Mackensen
Lehrstuhl für Innere Medizin V
Involved external institutions
United Kingdom (GB)How to cite
APA:
Resheq, Y.J., Li, K.-K., Ward, S.T., Wilhelm, A., Garg, A., Curbishley, S.M.,... Adams, D.H. (2015). Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells. Journal of Immunology, 194(6), 2578-86. https://doi.org/10.4049/jimmunol.1401046
MLA:
Resheq, Yazid J., et al. "Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells." Journal of Immunology 194.6 (2015): 2578-86.
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