| First Author | Schjenken JE | Year | 2020 |
| Journal | Mucosal Immunol | Volume | 13 |
| Issue | 4 | Pages | 609-625 |
| PubMed ID | 31988469 | Mgi Jnum | J:319615 |
| Mgi Id | MGI:6766115 | Doi | 10.1038/s41385-020-0255-0 |
| Citation | Schjenken JE, et al. (2020) MicroRNA miR-155 is required for expansion of regulatory T cells to mediate robust pregnancy tolerance in mice. Mucosal Immunol 13(4):609-625 |
| abstractText | 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. |
