MAIT Cells at the Fetal-Maternal Interface During Pregnancy

Kaipe, Helen; Raffetseder, Johanna; Ernerudh, Jan; Solders, Martin; Tiblad, Eleonor

doi:10.3389/fimmu.2020.01788

Cited by 19 publications

(22 citation statements)

References 79 publications

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“…Mucosal-associated invariant T (MAIT) cells are antimicrobial T cells able to recognize bacterial metabolites and can function as innate-like sensors and mediators of antiviral responses, playing also a role in the response to anticancer therapy 32 . MAIT cells accumulate at term pregnancy in the maternal blood that flows into the intervillous space inside the placenta, where they are recruited by chemotactic factors 33 . Patients with active COVID-19 infection displayed a decrease in circulating MAIT cell compartment that is characterized by strong activation 34 .…”

Section: Resultsmentioning

confidence: 99%

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

et al. 2021

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SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.

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Section: Resultsmentioning

confidence: 99%

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

et al. 2021

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“…Indeed, the local cell-to-cell concentrations may be higher than currently measurable levels, which could explain why most often supra-physiological concentrations are used in vitro. Furthermore, circulating maternal immune cells are sequestered in the placenta where they come in close contact with hormone-producing fetally-derived cells ( 67 ) and thus, have the potential of being exposed to much higher levels of P4 than in the peripheral circulation.…”

Section: Discussionmentioning

confidence: 99%

Progesterone Dampens Immune Responses in In Vitro Activated CD4+ T Cells and Affects Genes Associated With Autoimmune Diseases That Improve During Pregnancy

et al. 2021

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The changes in progesterone (P4) levels during and after pregnancy coincide with the temporary improvement and worsening of several autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis (RA). Most likely immune-endocrine interactions play a major role in these pregnancy-induced effects. In this study, we used next generation sequencing to investigate the direct effects of P4 on CD4+ T cell activation, key event in pregnancy and disease. We report profound dampening effects of P4 on T cell activation, altering the gene and protein expression profile and reversing many of the changes induced during the activation. The transcriptomic changes induced by P4 were significantly enriched for genes associated with diseases known to be modulated during pregnancy such as MS, RA and psoriasis. STAT1 and STAT3 were significantly downregulated by P4 and their downstream targets were significantly enriched among the disease-associated genes. Several of these genes included well-known and disease-relevant cytokines, such as IL-12β, CXCL10 and OSM, which were further validated also at the protein level using proximity extension assay. Our results extend the previous knowledge of P4 as an immune regulatory hormone and support its importance during pregnancy for regulating potentially detrimental immune responses towards the semi-allogenic fetus. Further, our results also point toward a potential role for P4 in the pregnancy-induced disease immunomodulation and highlight the need for further studies evaluating P4 as a future treatment option.

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“…Furthermore, we did not investigate functional responses of MAIT cells in 1 st trimester decidua. Studies on 3 rd trimester decidua showed MAIT cells to respond to bacterial challenge with the production of IFNγ, granzyme B and perforin, indicating potential involvement in antibacterial defenses ( 22 , 24 , 32 ). Given their tissue repair potential ( 8 ), also the transcriptional activity of MAIT cells would be relevant to investigate as well as their role in endometrial tissue remodeling during decidualization (in similarity to uterine NK cells).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, MAIT cells isolated from term decidua responded to bacterial challenge with production of IFNg, granzyme B and perforin at a similar magnitude as MAIT cells in peripheral blood (22). Furthermore, MAIT cells were found to be retained in the intervillous blood in term placenta; these cells responded to stimulation with the production of IFNg and cytotoxic effector molecules and could serve to defend the fetal-maternal interface from bacterial infections (22)(23)(24). In contrast, very little is known about MAIT cells in the early stage of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

MAIT Cells Balance the Requirements for Immune Tolerance and Anti-Microbial Defense During Pregnancy

et al. 2021

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Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset with proinflammatory and cytotoxic effector functions. During pregnancy, modulation of the maternal immune system, both at the fetal-maternal interface and systemically, is crucial for a successful outcome and manifests through controlled enhancement of innate and dampening of adaptive responses. Still, immune defenses need to efficiently protect both the mother and the fetus from infection. So far, it is unknown whether MAIT cells are subjected to immunomodulation during pregnancy, and characterization of decidual MAIT cells as well as their functional responses during pregnancy are mainly lacking. We here characterized the presence and phenotype of Vα7.2+CD161+ MAIT cells in blood and decidua (the uterine endometrium during pregnancy) from women pregnant in the 1st trimester, i.e., the time point when local immune tolerance develops. We also assessed the phenotype and functional responses of MAIT cells in blood of women pregnant in the 3rd trimester, i.e., when systemic immunomodulation is most pronounced. Multi-color flow cytometry panels included markers for MAIT subsets, and markers of activation (CD69, HLA-DR, Granzyme B) and immunoregulation (PD-1, CTLA-4). MAIT cells were numerically decreased at the fetal-maternal interface and showed, similar to other T cells in the decidua, increased expression of immune checkpoint markers compared with MAIT cells in blood. During the 3rd trimester, circulating MAIT cells showed a higher expression of CD69 and CD56, and their functional responses to inflammatory (activating anti-CD3/CD28 antibodies, and IL-12 and IL-18) and microbial stimuli (Escherichia coli, group B streptococci and influenza A virus) were generally increased compared with MAIT cells from non-pregnant women, indicating enhanced antimicrobial defenses during pregnancy. Taken together, our findings indicate dual roles for MAIT cells during pregnancy, with an evidently well-adapted ability to balance the requirements of immune tolerance in parallel with maintained antimicrobial defenses. Since MAIT cells are easily activated, they need to be strictly regulated during pregnancy, and failure to do so could contribute to pregnancy complications.

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MAIT Cells at the Fetal-Maternal Interface During Pregnancy

Cited by 19 publications

References 79 publications

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

Progesterone Dampens Immune Responses in In Vitro Activated CD4+ T Cells and Affects Genes Associated With Autoimmune Diseases That Improve During Pregnancy

MAIT Cells Balance the Requirements for Immune Tolerance and Anti-Microbial Defense During Pregnancy

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