Nucleated erythroid cells (NECs) are the precursors of erythrocytes. They can be found in various hematopoietic tissues or in the blood. Recently, they have been shown to be active players in immunosuppression through the synthesis of arginase-2 and reactive oxygen species. In this work, we studied NECs in adult bone marrow, umbilical cord blood, and foetal liver parenchyma using single-cell RNA sequencing and found that: (1) all studied NECs expressed the same set of genes, which was enriched in “GO biological process” immunity-related terms; (2) early and late NECs had differential expression of the genes associated with immunosuppression, cell cycle progression, apoptosis, and glycolysis; (3) NECs from different tissues of origin had differential expression of the genes associated with immunosuppression.
Erythroid cells are emerging players in immunological regulation that have recently been shown to play a crucial role in fetomaternal tolerance in mice. In this work, we set ourselves the goal of discovering additional information about the molecular mechanisms of this process. We used flow cytometry to study placental erythroid cells’ composition and BioPlex for the secretome profiling of 23 cytokines at E12.5 and E19.5 in both allogeneic and syngeneic pregnancies. We found that (1) placental erythroid cells are mainly represented by CD45+ erythroid cells; (2) the secretomes of CD71+ placental erythroid cells differ from the ones in syngeneic pregnancy; (3) CCL2, CCL3, CCL4 and CXCL1 chemokines were secreted on each day of embryonic development and in both types of pregnancy studied. We believe that these chemokines lure placental immune cells towards erythroid cells so that erythroid cells can induce anergy in those immune cells via cell-bound ligands such as PD-L1, enzymes such as ARG1, and secreted factors such as TGFβ-1.
Alternative splicing is a part of mRNA processing that expands the diversity of proteins encoded by a single gene. Studying the full range of proteins–products of translation of alternatively spliced mRNA is extremely important for understanding the interactions between receptor proteins and ligands since different receptor protein isoforms can provide variation in the activation of signaling pathways. In this study, we investigated the expression of isoforms of TNFR1 and TNFR2 receptors before and after exposure to TNFα in two cell lines that had previously demonstrated diverse effects on cell proliferation under TNFα incubation using RT-qPCR. We found that after incubation with TNFα: (1) expression of isoform 3 of the TNFRSF1A gene was increased in both cell lines; (2) the cell line with increased proliferation, K562, had decreased expression of isoforms 1 and 4 of the TNFRSF1A gene and expression of isoform 2 of TNFRSF1B gene was absent at all; (3) the cell line with decreased proliferation—MCF-7 had significantly increased expression of isoform 2 of TNFRSF1B gene. Thus, we can conclude that TNFα exposure to the K562 and MCF-7 cell lines leads to changes in the expression of TNFα receptor isoforms, which, in turn, can appear via diverse proliferative effects.
Иммунорегуляторная роль эритроидных ядросодержащих клетокФедеральное государственное бюджетное научное учреждение «Научно-исследовательский институт фундаментальной и клинической иммунологии» Министерства науки и высшего образования Российской Федерации, 630099, г. Новосибирск, Российская Федерация Резюме Эритроидные ядросодержащие клетки (ЭЯК) являются предшественницами самой массовой популяции клеток человека -эритроцитов, для которых была показана функция гемоиммунорегуляции на разных стадиях онтогенеза, в различных органах и тканях тела человека. ЭЯК осуществляют эту функцию при помощи секреции цитокинов, факторов роста, фермента аргиназы-2, АФК и при помощи поверхностных молекул PD-L1 и PD-L2. Показана их важная регуляторная роль в формировании фетоплацентарной иммуносупрессии, иммуносупрессии во время беременности, супрессии ответа против комменсалов в желудочно-кишечном тракте, в патогенезе бактериальных и вирусных инфекций взрослых, опухолевого роста и аутоиммунных заболеваний, а также участие в распознавании патоген-ассоциированных молекулярных паттернов при помощи Tollподобных рецепторов у рыб и птиц. Подобные качества вкупе с их количеством и широтой распространения представляют ЭЯК как активных участников множества процессов, что делает важным исследование их регуляторной роли в норме и при патологии.
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