Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells
Tomasz M. Grzywa, Anna Sosnowska, Zuzanna Rydzyńska, Michał Łaźniewski, Dariusz Plewczyński, Klaudia Klicka, Milena Małecka‐Giełdowska, Anna Rodziewicz-Lurzyńska, Olga Ciepiela, Magdalena Justyniarska, Paulina Pomper, Marcin Grzybowski, Roman Błaszczyk, Michał Węgrzynowicz, Agnieszka Tomaszewska, Grzegorz Basak, Jakub Gołąb, Dominika Nowis
Abstract
Abstract CD71 + erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-induced L -arginine depletion suppresses T-cell responses. In humans with anemia, CECs expand and express ARG1 and ARG2 that suppress T-cells IFN-γ production. Moreover, bone marrow CECs from healthy human donors suppress T-cells proliferation. CECs differentiated from peripheral blood mononuclear cells potently suppress T-cell activation, proliferation, and IFN-γ production in an ARG- and ROS-dependent manner. These effects are the most prominent for early-stage CECs (CD71 high CD235a dim cells). The suppressive properties disappear during erythroid differentiation as more differentiated CECs and mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of CECs in the immune response regulation.