TLRs induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface

Yu, Na; Weng, Yiming; Liu, Wei; Chen, Lixia; Yin, Zhe; He, Yongzhong; Wang, Yanqiu

doi:10.1016/j.intimp.2021.108070

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…In the present study, we observed a robust TARC upregulation in the PL of WT mice, which can be interpreted as a proactive response to safeguard pregnancy against inflammation. Further, the LPS challenge induces secretion of MCP-1 that shifts a balance between Th1 and Th2 cells resulting in an increased secretion of IL-4 and IL-10 and enhanced CD80 and CD86 expression at the feto-maternal interface [40]. LPS can also directly activate peritoneal B cells, stimulating Breg cell properties such as IL-10 and IL-6 secretion [41].…”

Section: Discussionmentioning

confidence: 99%

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Uehre,

Tchaikovski,

Ignatov

et al. 2023

IJMS

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The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19−/−, BMyD88−/− and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19−/−, BMyD88−/− and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.

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Section: Discussionmentioning

confidence: 99%

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Uehre,

Tchaikovski,

Ignatov

et al. 2023

IJMS

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“…Huang et al (2020)reported that human chorionic gonadotropin promoted the recruitment of regulatory T cells in the endometrium through increasing CCL2 levels in human ESCs. Yu et al (2021) revealed that Toll-like receptors induced Th1/ Th2 responses by affecting the CCL2 secretion of DSCs at the maternal-fetal interface.…”

Section: Ccl2/ccr2mentioning

confidence: 99%

Regulation and Function of Chemokines at the Maternal–Fetal Interface

Zhang

Ding

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Successful pregnancy requires the maternal immune system to tolerate the semi-allogeneic embryo. A good trophoblast function is also essential for successful embryo implantation and subsequent placental development. Chemokines are initially described in recruiting leukocytes. There are rich chemokines and chemokine receptor system at the maternal–fetal interface. Numerous studies have reported that they not only regulate trophoblast biological behaviors but also participate in the decidual immune response. At the same time, the chemokine system builds an important communication network between fetally derived trophoblast cells and maternally derived decidual cells. However, abnormal functions of chemokines or chemokine receptors are involved in a series of pregnancy complications. As growing evidence points to the roles of chemokines in pregnancy, there is a great need to summarize the available data on this topic. This review aimed to describe the recent research progress on the regulation and function of the main chemokines in pregnancy at the maternal–fetal interface. In addition, we also discussed the potential relationship between chemokines and pregnancy complications.

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“…Toll-like receptors (TLRs), primarily TLR4, play an important role in Th1/Th2 immune responses [ 14 ]. TLR4 is one of the best characterized innate immune receptors and can induce excessive macrophage inflammatory responses [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal–fetal interface

Lou

Tian

et al. 2023

Reprod Biol Endocrinol

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Background Decidual macrophages participate in immune regulation at the maternal–fetal interface. Abnormal M1/M2 polarization of decidual macrophages might predispose immune maladaptation in recurrent pregnancy loss (RPL). However, the mechanism of decidual macrophage polarization is unclear. We explored the role of Estradiol (E2)-sensitive serum-glucocorticoid regulated kinase (SGK) 1 in promoting macrophage polarization and suppressing inflammation at the maternal–fetal interface. Methods We assessed serum levels of E2 and progesterone during first trimester of pregnancy in women with or without threatened miscarriages (ended in live birth, n = 448; or early miscarriages, n = 68). For detection of SGK1 in decidual macrophages, we performed immunofluorescence labeling and western blot analysis applying decidual samples from RPL (n = 93) and early normal pregnancy (n = 66). Human monocytic THP-1 cells were differentiated into macrophages and treated with Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), E2, inhibitors or siRNA for in vitro analysis. Flow cytometry analysis were conducted to detect macrophages polarization. We also applied ovariectomized (OVX) mice with hormones exploring the mechanisms underlying the regulation of SGK1 activation by E2 in the decidual macrophages in vivo. Results SGK1 expression down regulation in the decidual macrophages of RPL was consistent with the lower concentration and slower increment of serum E2 from 4 to 12 weeks of gestation seen in these compromised pregnancies. LPS reduced SGK1 activities, but induced the pro-inflammatory M1 phenotype of THP-1 monocyte-derived macrophages and T helper (Th) 1 cytokines that favored pregnancy loss. E2 pretreatment promoted SGK1 activation in the decidual macrophages of OVX mice in vivo. E2 pretreatment amplified SGK1 activation in TLR4-stimulated THP-1 macrophages in vitro through the estrogen receptor beta (ERβ) and PI3K pathway. E2-sensitive activation of SGK1 increased M2 macrophages and Th2 immune responses, which were beneficial to successful pregnancy, by inducing ARG1 and IRF4 transcription, which are implicated in normal pregnancy. The experiments on OVX mice have shown that pharmacological inhibition of E2 promoted nuclear translocation of NF-κB in the decidual macrophages. Further more, pharmacological inhibition or knockdown of SGK1 in TLR4-stimulated THP-1 macrophages activated NF-κB by promoting its nuclear translocation, leading to increased secretion of pro-inflammatory cytokines involved in pregnancy loss. Conclusion Our findings highlighted the immunomodulatory roles of E2-activated SGK1 in Th2 immune responses by priming anti-inflammatory M2 macrophages at the maternal–fetal interface, resulting in a balanced immune microenvironment during pregnancy. Our results suggest new perspectives on future preventative strategies for RPL.

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TLRs induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface

Cited by 5 publications

References 27 publications

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Regulation and Function of Chemokines at the Maternal–Fetal Interface

Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal–fetal interface

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