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https://hdl.handle.net/2440/124158
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dc.contributor.author | Schjenken, J.E. | - |
dc.contributor.author | Moldenhauer, L.M. | - |
dc.contributor.author | Zhang, B. | - |
dc.contributor.author | Care, A.S. | - |
dc.contributor.author | Groome, H.M. | - |
dc.contributor.author | Chan, H.Y. | - |
dc.contributor.author | Hope, C.M. | - |
dc.contributor.author | Barry, S.C. | - |
dc.contributor.author | Robertson, S.A. | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Mucosal Immunology, 2020; 13(4):609-625 | - |
dc.identifier.issn | 1933-0219 | - |
dc.identifier.issn | 1935-3456 | - |
dc.identifier.uri | http://hdl.handle.net/2440/124158 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | 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 | - |
dc.language.iso | en | - |
dc.publisher | Springer Nature | - |
dc.rights | © Society for Mucosal Immunology 2020 | - |
dc.source.uri | http://dx.doi.org/10.1038/s41385-020-0255-0 | - |
dc.subject | Uterus | - |
dc.subject | Lymph Nodes | - |
dc.subject | T-Lymphocyte Subsets | - |
dc.subject | Animals | - |
dc.subject | Mice | - |
dc.subject | Abortion, Spontaneous | - |
dc.subject | MicroRNAs | - |
dc.subject | Cytokines | - |
dc.subject | Immunohistochemistry | - |
dc.subject | Immunophenotyping | - |
dc.subject | Lymphocyte Activation | - |
dc.subject | Immune Tolerance | - |
dc.subject | Gene Expression Regulation | - |
dc.subject | Gestational Age | - |
dc.subject | Pregnancy | - |
dc.subject | Female | - |
dc.subject | T-Lymphocytes, Regulatory | - |
dc.subject | Gene Knockdown Techniques | - |
dc.subject | Immunomodulation | - |
dc.subject | Biomarkers | - |
dc.title | MicroRNA miR-155 is required for expansion of regulatory T cells to mediate robust pregnancy tolerance in mice | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/s41385-020-0255-0 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1041335 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/109219 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/160102366 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Schjenken, J.E. [0000-0001-6293-6160] | - |
dc.identifier.orcid | Moldenhauer, L.M. [0000-0002-3141-2521] | - |
dc.identifier.orcid | Care, A.S. [0000-0002-0943-9453] | - |
dc.identifier.orcid | Groome, H.M. [0000-0002-6087-0409] | - |
dc.identifier.orcid | Chan, H.Y. [0000-0001-9841-2094] | - |
dc.identifier.orcid | Hope, C.M. [0000-0001-8206-1939] | - |
dc.identifier.orcid | Barry, S.C. [0000-0002-0597-7609] | - |
dc.identifier.orcid | Robertson, S.A. [0000-0002-9967-0084] | - |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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