The role of CD71+ erythroid cells in the regulation of the immune response

Tomasz M Grzywa; Dominika Nowis; Jakub Golab

doi:10.1016/j.pharmthera.2021.107927

The role of CD71⁺ erythroid cells in the regulation of the immune response

Pharmacol Ther. 2021 Dec:228:107927. doi: 10.1016/j.pharmthera.2021.107927. Epub 2021 Jun 24.

Authors

Tomasz M Grzywa¹, Dominika Nowis², Jakub Golab³

Affiliations

¹ Department of Immunology, Medical University of Warsaw, Nielubowicza 5 Street, 02-097 Warsaw, Poland; Doctoral School, Medical University of Warsaw, Zwirki and Wigury 61 Street, 02-091 Warsaw, Poland; Laboratory of Experimental Medicine, Medical University of Warsaw, Nielubowicza 5 Street, 02-097 Warsaw, Poland. Electronic address: tomasz.grzywa@wum.edu.pl.
² Department of Immunology, Medical University of Warsaw, Nielubowicza 5 Street, 02-097 Warsaw, Poland; Laboratory of Experimental Medicine, Medical University of Warsaw, Nielubowicza 5 Street, 02-097 Warsaw, Poland. Electronic address: dominika.nowis@wum.edu.pl.
³ Department of Immunology, Medical University of Warsaw, Nielubowicza 5 Street, 02-097 Warsaw, Poland; Centre of Preclinical Research, Medical University of Warsaw, Banacha 1b Street, 02-097 Warsaw, Poland. Electronic address: jakub.golab@wum.edu.pl.

PMID: 34171326
DOI: 10.1016/j.pharmthera.2021.107927

Abstract

Complex regulation of the immune response is necessary to support effective defense of an organism against hostile invaders and to maintain tolerance to harmless microorganisms and autoantigens. Recent studies revealed previously unappreciated roles of CD71⁺ erythroid cells (CECs) in regulation of the immune response. CECs physiologically reside in the bone marrow where erythropoiesis takes place. Under stress conditions, CECs are enriched in some organs outside of the bone marrow as a result of extramedullary erythropoiesis. However, the role of CECs goes well beyond the production of erythrocytes. In neonates, increased numbers of CECs contribute to their vulnerability to infectious diseases. On the other side, neonatal CECs suppress activation of immune cells in response to abrupt colonization with commensal microorganisms after delivery. CECs are also enriched in the peripheral blood of pregnant women as well as in the placenta and are responsible for the regulation of feto-maternal tolerance. In patients with cancer, anemia leads to increased frequency of CECs in the peripheral blood contributing to diminished antiviral and antibacterial immunity, as well as to accelerated cancer progression. Moreover, recent studies revealed the role of CECs in HIV and SARS-CoV-2 infections. CECs use a full arsenal of mechanisms to regulate immune response. These cells suppress proinflammatory responses of myeloid cells and T-cell proliferation by the depletion of ʟ-arginine by arginase. Moreover, CECs produce reactive oxygen species to decrease T-cell proliferation. CECs also secrete cytokines, including transforming growth factor β (TGF-β), which promotes T-cell differentiation into regulatory T-cells. Here, we comprehensively describe the role of CECs in orchestrating immune response and indicate some therapeutic approaches that might be used to regulate their effector functions in the treatment of human conditions.

Keywords: CD71(+) erythroid cells; Erythroid progenitor cells; Erythropoiesis; Immune response; Immunoregulation; Immunosuppression.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antigens, CD* / physiology
COVID-19
Erythroid Cells* / metabolism
Humans
Immunity* / physiology
Receptors, Transferrin* / physiology

Substances

Antigens, CD
CD71 antigen
Receptors, Transferrin