CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

Abstract

Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of pro-inflammatory cytokines and a reduction in the release of TGFβ. Moreover, PTL-derived neonatal CD71+ erythroid cells: 1) modestly altered CD8+ T cell activation; 2) inhibited conventional CD4+ and CD8+ T-cell expansion; 3) suppressed the expansion of CD8+ regulatory T cells,; 4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and 5) indirectly modulated T-cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal T-cell and myeloid responses and their direct contact with maternal mononuclear cells induces a pro-inflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor.

CD71+ Erythroid Suppressor Cells Promote Fetomaternal Tolerance through Arginase-2 and PDL-1

“…In agreement, a very recent report indicated that CD71 + erythroid cells from human cord blood inhibited CD4 + and CD8 + T cells proliferation and reduced CD62L expression in activated T cells (27). In contrast, this study claimed that CD71 + erythroid cells enhanced proinflammatory cytokine production in vitro (27). The explanation for this discrepancy might be due to multiple factors such as the study population (African American women versus white women), using different bacterial strains for the cell stimulation, and isolation techniques for CD71 + erythroid cells (positive versus negative selection).…”

“…Furthermore, we have shown that CD71 + erythroid cells form full-term cord blood specimens, have immunosuppressive properties, and suppress proinflammatory cytokines (IL-6 and TNF-a) by myeloid cells (23) and also inhibit T cell proliferation (24). In agreement, a very recent report indicated that CD71 + erythroid cells from human cord blood inhibited CD4 + and CD8 + T cells proliferation and reduced CD62L expression in activated T cells (27). In contrast, this study claimed that CD71 + erythroid cells enhanced proinflammatory cytokine production in vitro (27).…”

Prenatal Maternal Stress Causes Preterm Birth and Affects Neonatal Adaptive Immunity in Mice

“…Growing evidence shows that neonatal immunity depends on the critical immunosuppressive function of CD71+ nucleated erythroid cells (60)(61)(62)(63)(64)(65). Indeed, we have shown that cord blood CD71+ erythroid cells play a central role in the modulation of inflammatory responses of neonates, which may be defective in those delivered prematurely (66,67). Therefore, we investigated whether prenatal maternal stress alters the number of CD71+ erythroid cells in neonates (Figure 6A).…”

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study

“…CD71+ erythroid cells have immunomodulatory functions on cord blood leukocytes (157)(158)(159), and that their direct contact with maternal peripheral immune cells increases the secretion of pro-inflammatory mediators by such cells (159). Therefore, it is likely that the trafficking of CD71+ erythroid cells from the fetus into the mother directly affects maternal immune responses (159).…”