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Type: Journal article
Title: MicroRNA miR-155 is required for expansion of regulatory T cells to mediate robust pregnancy tolerance in mice
Author: Schjenken, J.E.
Moldenhauer, L.M.
Zhang, B.
Care, A.S.
Groome, H.M.
Chan, H.-.Y.
Hope, C.M.
Barry, S.C.
Robertson, S.A.
Citation: Mucosal Immunology, 2020; 13(4):609-625
Publisher: Springer Nature
Issue Date: 2020
ISSN: 1933-0219
Statement of
John E. Schjenken, Lachlan M. Moldenhauer, Bihong Zhang, Alison S. Care, Holly M. Groome, Hon-Yeung Chan, Christopher M. Hope, Simon C. Barry and Sarah A. Robertson
Abstract: The immune-regulatory microRNA miR-155 is reduced in recurrent miscarriage, suggesting that miR-155 contributes to immune tolerance in pregnancy. Here we show miR-155 is induced in the uterine mucosa and draining lymph nodes (dLN) during the female immune response to male seminal fluid alloantigens. Mice with null mutation in miR-155 (miR-155-/-) exhibited a reduced CD4+ T cell response after mating, with a disproportionate loss of CD25+FOXP3+ Treg cells. miR-155 deficiency impaired expansion of both peripheral and thymic Treg cells, distinguished by neuropilin-1 (NRP1), and fewer Treg cells expressed Ki67 proliferation marker and suppressive function marker CTLA4. Altered Treg phenotype distribution in miR-155-/- mice was confirmed by t-distributed neighbor embedding (tSNE) analysis. Fewer dendritic cells (DCs) and macrophages trafficked to the dLN of miR-155-/- mice, associated with lower CCR7 on DCs, and reduced uterine Ccl19 expression, implicating compromised antigen presentation in the stunted Treg cell response. miR-155-/- mice exhibited elevated susceptibility to inflammation-induced fetal loss and fetal growth restriction compared with miR-155+/+ controls, but outcomes were restored by transfer of wild-type Tregs. Thus miR-155 is a key regulator of immune adaptation to pregnancy and is necessary for sufficient Tregs to achieve robust pregnancy tolerance and protect against fetal loss.
Rights: © Society for Mucosal Immunology 2020
RMID: 1000012913
DOI: 10.1038/s41385-020-0255-0
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