Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Liu, Qian; Tian, Fu‐Ju; Xie, Qingzhen; Zhang, Jun; Liu, Liu; Yang, Jing

doi:10.1111/aji.12498

Cited by 7 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As reported, no matter whether in patients suffering from spontaneous abortion or LPS‐injected murine models, increased serum levels of IL‐17A, expansion of CD4 + IL17A + T cells in the peripheral blood and spleen and infiltration of Th17 cells into the maternal‐fetal interface are observed 48,49 . Our study also found the same results.…”

Section: Discussionsupporting

confidence: 90%

CaMK4 promotes abortion‐related Th17 cell imbalance by activating AKT/mTOR signaling pathway

Chang

Yin

et al. 2020

American J Rep Immunol

Self Cite

View full text Add to dashboard Cite

Problem: The balance of the immune microenvironment along the maternal-fetal interface is closely related to pregnancy outcomes, with excessive inflammatory reactions leading to the occurrence of pathological pregnancy outcomes such as abortion. CaMK4 has been reported to play a significant role in autoimmune diseases through the regulation of Th17 cells. However, whether CaMK4 is associated with spontaneous abortion or the immune microenvironment along the maternal-fetal interface remains unclear. Methods of study: In this study, we constructed normal pregnancy and LPS-induced abortion models in mice, and a CaMK4 inhibitor called KN-93 was administered to investigate the changes in and mechanisms of the immune response. The expression of CaMK4 was evaluated in the uteroplacental complex and spleen. Furthermore, the infiltration and function of Th17 cells were estimated in peripheral tissues and the uteroplacental complex. Results: The expression of CaMK4 in the uteroplacental complex and spleen was significantly higher in the LPS-treated group than in the normal pregnancy group. KN-93, the CaMK4 inhibitor, reversed fetal resorption and excessive inflammation. In detail, KN-93 led to reduced infiltration of Th17 cells into peripheral tissues and the uteroplacental complex, and the functions of Th17 cells were inhibited. In addition, CaMK4 promoted the AKT/mTOR signaling pathway, which is one of the mechanisms that regulate the immune microenvironment. Conclusion: CaMK4 is a critical regulator that promotes the expansion of Th17 cells and enhances their functions through the AKT/mTOR signaling pathway. The inhibition of CaMK4 can reverse the immune imbalance along the maternal-fetal interface and improve pregnancy outcomes.

show abstract

Section: Discussionsupporting

confidence: 90%

CaMK4 promotes abortion‐related Th17 cell imbalance by activating AKT/mTOR signaling pathway

Chang

Yin

et al. 2020

American J Rep Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the AMD1 protein was located in luminal and epithelial cells of bovine endometrium [43]. This window also harbors FYN associated with mouse oocyte maturation [44] and maternal-fetal immune tolerance in humans and mice [45], REV3L which contributes to genome stability during neoplastic transformation and progression in mice—targeted disruption of this gene results in lethality during midgestation [46, 47], and SLC16A10 which is differentially expressed in human placenta at mid-gestation, regulating embryonic development and growth [48]. Window 70-71Mb of BTA 17 was significant for both traits.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study provides strong evidence of genes affecting the reproductive performance of Nellore beef cows

et al. 2017

View full text Add to dashboard Cite

Reproductive traits are economically important for beef cattle production; however, these traits are still a bottleneck in indicine cattle since these animals typically reach puberty at older ages when compared to taurine breeds. In addition, reproductive traits are complex phenotypes, i.e., they are controlled by both the environment and many small-effect genes involved in different pathways. In this study, we conducted genome-wide association study (GWAS) and functional analyses to identify important genes and pathways associated with heifer rebreeding (HR) and with the number of calvings at 53 months of age (NC53) in Nellore cows. A total of 142,878 and 244,311 phenotypes for HR and NC53, respectively, and 2,925 animals genotyped with the Illumina Bovine HD panel (Illumina®, San Diego, CA, USA) were used in GWAS applying the weighted single-step GBLUP (WssGBLUP) method. Several genes associated with reproductive events were detected in the 20 most important 1Mb windows for both traits. Significant pathways for HR and NC53 were associated with lipid metabolism and immune processes, respectively. MHC class II genes, detected on chromosome 23 (window 25-26Mb) for NC53, were significantly associated with pregnancy success of Nellore cows. These genes have been proved previously to be associated with reproductive traits such as mate choice in other breeds and species. Our results suggest that genes associated with the reproductive traits HR and NC53 may be involved in embryo development in mammalian species. Furthermore, some genes associated with mate choice may affect pregnancy success in Nellore cattle.

show abstract

“…In a consistent manner, the functional enrichment analysis of hub genes in placental villi showed that the regulated genes were mainly related to the regulation of cell proliferation, angiogenesis, cell migration, and focal adhesion, which are important processes involved in placental and fetal development. Studies have demonstrated that FYN expression, which is elevated at the fetomaternal interface of abortion-prone mice and RPL patients, plays a role in the regulation of fetomaternal immune tolerance by encouraging the expansion of Th17 cells and the expression of proinflammatory factors (Khan et al, 2014;Liu et al, 2016). A FYN inhibitor overcomes the aberrant inflammatory state and embryo resorption caused by LPS (Liu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of circulating microRNAs and the placental transcriptome in recurrent pregnancy loss

Zhou

Shi

et al. 2022

Front. Physiol.

View full text Add to dashboard Cite

Recurrent pregnancy loss (RPL) is a major type of pathological pregnancy that still lacks reliable early diagnosis and effective treatment. The placenta is critical to fetal development and pregnancy success because it participates in critical processes such as early embryo implantation, vascular remodeling, and immunological tolerance. RPL is associated with abnormalities in the biological behavior of placental villous trophoblasts, resulting in aberrant placental function. MicroRNAs (miRNAs) are increasingly being recognized as essential regulators of placental development, as well as potential biomarkers. In this study, plasma miRNAs and placental messenger RNAs (mRNAs) from RPL patients and normal pregnant (NP) controls were sequenced and analyzed. Compared to those in NP controls, 108 circulating miRNAs and 1199 placental mRNAs were differentially expressed in RPL samples. A total of 140 overlapping genes (overlapping between plasma miRNA target genes and actual placental disorder genes) were identified, and functional enrichment analysis showed that these genes were mainly related to cell proliferation, angiogenesis, and cell migration. The regulatory network among miRNAs, overlapping genes, and downstream biological processes was analyzed by protein–protein interactions and Cytoscape. Moreover, enriched mRNAs, which were predictive targets of the differentially expressed plasma miRNAs miR-766-5p, miR-1285-3p, and miR-520a-3p, were accordingly altered in the placenta. These results suggest that circulating miRNAs may be involved in the pathogenesis of RPL and are potential noninvasive biomarkers for RPL.

show abstract

Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Abstract: Fyn is confirmed as a negative regulator in fetomaternal immune tolerance, through promoting Th17 cell expansion and proinflammatory factors expression.

Cited by 7 publications

References 40 publications

CaMK4 promotes abortion‐related Th17 cell imbalance by activating AKT/mTOR signaling pathway

CaMK4 promotes abortion‐related Th17 cell imbalance by activating AKT/mTOR signaling pathway

Genome-wide association study provides strong evidence of genes affecting the reproductive performance of Nellore beef cows

Integrative analysis of circulating microRNAs and the placental transcriptome in recurrent pregnancy loss

Contact Info

Product

Resources

About