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https://hdl.handle.net/2440/124158
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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 1935-3456 |
Statement of Responsibility: | 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. |
Keywords: | Uterus Lymph Nodes T-Lymphocyte Subsets Animals Mice Abortion, Spontaneous MicroRNAs Cytokines Immunohistochemistry Immunophenotyping Lymphocyte Activation Immune Tolerance Gene Expression Regulation Gestational Age Pregnancy Female T-Lymphocytes, Regulatory Gene Knockdown Techniques Immunomodulation Biomarkers |
Rights: | © Society for Mucosal Immunology 2020 |
DOI: | 10.1038/s41385-020-0255-0 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1041335 http://purl.org/au-research/grants/nhmrc/109219 http://purl.org/au-research/grants/nhmrc/160102366 |
Published version: | http://dx.doi.org/10.1038/s41385-020-0255-0 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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