Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy

Sayama, Seisuke; Nagamatsu, Takeshi; Schust, Danny J.; Itaoka, Naoko; Ichikawa, Masao; Kawana, Kei; Yamashita, Takahiro; Kozuma, Shiro; Fujii, Tomoyuki

doi:10.1016/j.jri.2013.08.001

Cited by 53 publications

(34 citation statements)

References 36 publications

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“…For example, decidual macrophages are able to inhibit NK cell cytotoxicity (Co et al, 2013), to suppress T cell proliferation and activation (Mizuno et al, 1994;Sayama et al, 2013) and to induce Treg cells (Vacca et al, 2010;Hsu et al, 2012), which our results further support. Also decidual stromal cells have been shown to contribute to limited T cell activation and induction of Treg cells (Nagamatsu et al, 2009;Erkers et al, 2013).…”

Section: Macrophages Th Cells and Treg Cellssupporting

confidence: 83%

“…However, allogeneic T cells co-cultured with decidual macrophages produced much lower levels of Th1-associated IFN-γ, as compared with T cells co-cultured with blood monocytes (Sayama et al, 2013). Although Th1 cells were not specifically analyzed, this study (Tilburgs et al, 2006;Mjosberg et al, 2010).…”

Section: Influence Of Decidual Macrophages On the Polarization Of Th1mentioning

confidence: 88%

“…Another observation indicating an immune regulatory function of decidual macrophages was their role in the clearance of apoptotic cells (Mor and Abrahams, 2003). It is only recently that the function of human decidual macrophages has been studied in more detail, and several reports now suggest that decidual macrophages influence the function of both decidual NK cells and T cells (Vacca et al, 2010;Co et al, 2013;Sayama et al, 2013). The function of decidual macrophages is likely controlled by epigenetic mechanisms; in particular, genes encoding M1-associated factors (for instance IL-1β and the IL-12 receptor β2 subunit) are hypermethylated, while genes encoding M2-associated factors (for instance A2M and IL-10) are hypomethylated, suggesting a predisposition towards an immune regulatory phenotype .…”

Section: Phenotype and Function Of Decidual Macrophagesmentioning

confidence: 99%

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Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Svensson‐Arvelund¹

2015

Linköping University Medical Dissertations

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A successful pregnancy requires that the maternal immune system adapts to tolerate the semi-allogeneic fetal-placental unit. This adaptation mainly occurs locally, i.e. at the fetal-maternal interface, where fetal-derived tissues come into close contact with maternal cells in the uterine endometrium (called decidua during pregnancy). decidual macrophages preferentially secreted the monocyte-and Treg cell-associated chemokines CCL2 and CCL18, while Th1-, Th2-and Th17-related chemokines were produced at low levels. These results suggest that decidual macrophages contribute to create the unique decidual cell composition and a tolerogenic immune environment that is compatible with fetal development. Further, by comparing decidual macrophages with different in vitro macrophage subsets, we showed that M-CSF and

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Section: Macrophages Th Cells and Treg Cellssupporting

confidence: 83%

Section: Influence Of Decidual Macrophages On the Polarization Of Th1mentioning

confidence: 88%

Section: Phenotype and Function Of Decidual Macrophagesmentioning

confidence: 99%

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Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Svensson‐Arvelund¹

2015

Linköping University Medical Dissertations

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“…This includes induction of Tregs and suppression of T cell activation by decidual macrophages (12,14) and stromal cells (32,33), as well as the induction of Tregs through the interaction between decidual macrophages and uterine NK cells (13). However, our novel findings show that placental-derived factors directly promote differentiation of homeostatic M2 macrophages and expansion of Tregs while limiting Th cell activation, indicating that fetal-derived tissue itself is a main inducer of maternal immune cell adaptation.…”

Section: Foxp3mentioning

confidence: 69%

“…Human decidual macrophages have properties predominantly associated with homeostatic M2 macrophages, including expression of the homeostatic scavenger receptor CD163 and the pattern recognition receptors CD206 and CD209, as well as the preferential production of cytokines and chemokines like IL-10, CCL2, and CCL18 (6)(7)(8)(9)(10)(11). Decidual macrophages are also functionally regulatory, being able to suppress the production of IFN-g by T cells (12) and to induce Tregs in vitro (13,14). Tregs are essential to the establishment and maintenance of pregnancy, as shown by murine studies (15,16).…”

mentioning

confidence: 99%

The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages

Svensson‐Arvelund

Mehta

Lindau

et al. 2015

The Journal of Immunology

261

247

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A successful pregnancy requires that the maternal immune system is instructed to a state of tolerance to avoid rejection of the semiallogeneic fetal-placental unit. Although increasing evidence supports that decidual (uterine) macrophages and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not known how these tolerogenic leukocytes are induced. In this article, we show that the human fetal placenta itself, mainly through trophoblast cells, is able to induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10 induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23. Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs in parallel with increased IL-10 production, whereas production of IFN-gamma (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the suppressive markers CTLA-4 and CD39, were functionally suppressive, and were induced, in part, by IL-10, TGF-beta, and TRAIL. Placental-derived factors also limited excessive Th cell activation, as shown by decreased HLA-DR expression and reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data indicate that the fetal placenta has a central role in promoting the homeostatic environment necessary for successful pregnancy. These findings have implications for immune-mediated pregnancy complications, as well as for our general understanding of tissue-induced tolerance.

Funding Agencies|Medical Research Council [K2013-61X-22310-01-4]

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Generating Functional Multicellular Organoids from Human Placenta Villi

Huang

Liang

et al. 2023

Advanced Science

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The interaction between trophoblasts, stroma cells, and immune cells at the maternal–fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air–liquid surface culture is developed. PVOs contain cytotrophoblasts that can self‐renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO‐based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta‐originated diseases.

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Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy

Cited by 53 publications

References 36 publications

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages

Generating Functional Multicellular Organoids from Human Placenta Villi

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