Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy.

Abstract:

:Although neutrophils are known to be fundamental in controlling innate immune responses, their role in regulating adaptive immunity is just starting to be appreciated. We report that human neutrophils exposed to pregnancy hormones progesterone and estriol promote the establishment of maternal tolerance through the induction of a population of CD4+ T cells displaying a GARP+CD127loFOXP3+ phenotype following antigen activation. Neutrophil-induced T (niT) cells produce IL-10, IL-17, and VEGF and promote vessel growth in vitro. Neutrophil depletion during murine pregnancy leads to abnormal development of the fetal-maternal unit and reduced empbryo development, with placental architecture displaying poor trophoblast invasion and spiral artery development in the maternal decidua, accompanied by significantly attenuated niT cell numbers in draining lymph nodes. Using CD45 congenic cells, we show that induction of niT cells and their regulatory function occurs via transfer of apoptotic neutrophil-derived proteins, including forkhead box protein 1 (FOXO1), to T cells. Unlike in women with healthy pregnancies, neutrophils from blood and placental samples of preeclamptic women fail to induce niT cells as a direct consequence of their inability to transfer FOXO1 to T cells. Finally, neutrophil-selective FOXO1 knockdown leads to defective placentation and compromised embryo development, similar to that resulting from neutrophil depletion. These data define a nonredundant function of neutrophil-T cell interactions in the regulation of vascularization at the maternal-fetal interface.

authors

Nadkarni S,Smith J,Sferruzzi-Perri AN,Ledwozyw A,Kishore M,Haas R,Mauro C,Williams DJ,Farsky SH,Marelli-Berg FM,Perretti M

doi

10.1073/pnas.1611944114

subject

Has Abstract

pub_date

2016-12-27 00:00:00

pages

E8415-E8424

issue

52

eissn

0027-8424

issn

1091-6490

pii

1611944114

journal_volume

113

pub_type

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