4.7 Article

Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells

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COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s42003-021-02914-4

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资金

  1. Polish Ministry of Education and Science [013/RID/2018/19]
  2. National Science Center in Poland [2019/35/B/NZ6/00540, 2017/25/B/NZ6/01139, 2016/23/B/NZ6/03463, 2019/35/O/ST6/02484, 2020/37/B/NZ2/03757]
  3. TEAM program from the Foundation for Polish Science
  4. European Union
  5. IDUB against COVID-19 project project by the Warsaw University of Technology under the program Excellence Initiative: Research University (IDUB)

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The study shows that early CD71+ erythroid cells expand in the spleen of anemic mice and humans, utilizing high levels of arginase 2 (ARG2) and reactive oxygen species (ROS) to suppress T-cell activation. These findings provide insight into the regulatory role of CECs in the immune response.
Grzywa et al. show that early CD71+ erythroid cells expand in the spleen of anemic mice and in humans and suppress T-cell activation. These results provide insight into the role of CECs in the immune response regulation. 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-gamma 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-gamma 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.

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