Arginase-1 is neither constitutively expressed in nor required for myeloid-derived suppressor cell-mediated inhibition of T-cell proliferation

European Journal of Immunology
Zhen BianYuan Liu

Abstract

Although previous reports suggest that tumor-induced myeloid-derived suppressor cells (MDSC) inhibit T cells by L-arginine depletion through arginase-1 activity, we herein show that arginase-1 is neither inherently expressed in MDSC nor required for MDSC-mediated inhibition. Employing Percoll density gradients, large expansions of MDSC in the bone marrow of tumor-bearing mice were isolated and demonstrated potent inhibition in T-cell proliferation activated by TCR-ligation, Concanavalin A, PMA plus ionomycin, or IL-2. Despite demonstrating characteristic immunosuppressive capacity, these MDSC exhibit no arginase-1 expression and/or exert their inhibitory effects independent of arginase-1 activity. However, arginase-1 expression in MDSC can be induced by exposure to TCR-activated T cells or their culture medium, but not T cells activated by other means or growing tumor cells. Further investigation reveals multiple cytokines secreted by TCR-activated T cells as orchestrating two signaling-relay axes, IL-6-to-IL-4 and GM-CSF/IL-4-to-IL-10, leading to arginase-1 expression in MDSC. Specifically, IL-6 signaling increases IL-4R, enabling IL-4 to induce arginase-1 expression; similarly, GM-CSF in concert with IL-4 induces IL-10R, allo...Continue Reading

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Citations

Feb 13, 2020·Parasite Immunology·Klaudia K BrodaczewskaMaria Doligalska
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May 1, 2021·Journal of Clinical Medicine·Alejandro Olivares-HernándezJosé Pablo Miramontes-González
Jun 4, 2020·Cellular Oncology (Dordrecht)·Łukasz ZadkaPiotr Dzięgiel
Jul 3, 2021·Journal of Clinical Medicine·Christophe VanhaverAnnika M Bruger
Nov 26, 2021·Expert Review of Anticancer Therapy·Fateme SheidaNima Rezaei

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