Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions

Hou, Ren; Huang, Renliang; Zhou, Yue; Lin, Dong; Xu, Jing; Yang, Liuqing; Wei, Xiaolan; Xie, Zhouqing; Zhou, Qiaomiao

doi:10.1016/j.fertnstert.2022.12.016

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…It would thus be interesting to evaluate whether IL-35, known to be overexpressed in cancers 30,33,45,54 , plays a role in the NK conversion into ILC1-like cells in cancers. Moreover, this ILC1like phenotype is shared with decidual NK cells (dNK) [55][56][57] that display reduced cytotoxicity and production of IFN-γ and TNF-α compared to circulating NK cells and express pro-angiogenic factors 55,[57][58][59][60] . Thus, it is tempting to speculate that dNK actually represent ILC1-like converted NK cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Bendriss-Vermare,

Picant,

Revol-Bauz

et al. 2024

Preprint

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Natural Killer (NK) cells lose their effector functions towards dangerous cells in chronic inflammatory diseases through still elusive mechanisms. Here, we demonstrate that Interleukin 35 (IL-35), an immunosuppressive member of the IL-12 family, inhibits human NK cell proliferation, pro-inflammatory, and cytotoxic functions, while promoting their secretion of TGF-β and proangiogenic factors. Furthermore, prolonged exposure to IL-35 converts NK cells into ILC1-like cells with tissue residency features (CD9+CD103+CD49a+) and low effector functions, that was dependent on autocrine TGF-β. Single cell RNAseq analysis also revealed an ILC1-like heterogeneity associated to the initial NK subpopulation, conventional or adaptive, undergoing the conversion. Overall, our findings identify a new role of IL-35 as a key driver of NK cell plasticity leading to the acquisition of tissue residency features and weakened effector functions that might play a role in physiopathological contexts and represent an attractive target for future immunotherapies to improve NK cell clinical activity.

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Section: Discussionmentioning

confidence: 99%

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Bendriss-Vermare,

Picant,

Revol-Bauz

et al. 2024

Preprint

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“…[4][5][6][7] Moreover, in individuals with RSA, uterine natural killer cells exhibit reduced capacity to clear senescent endometrial stromal cells, while their cytotoxicity against non-senescent cells is enhanced. 30 The above factors collectively contribute to an unfavorable maternal microenvironment for fetal development. Herein, we investigated the role of CBLL1 in endometrial stromal through ubiquitination, 10,31 which seems to contradict with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…The aged endometrium exhibits significantly reduced receptivity and impaired decidualization capacity 4–7 . Moreover, in individuals with RSA, uterine natural killer cells exhibit reduced capacity to clear senescent endometrial stromal cells, while their cytotoxicity against non‐senescent cells is enhanced 30 . The above factors collectively contribute to an unfavorable maternal microenvironment for fetal development.…”

Section: Discussionmentioning

confidence: 99%

CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion

Liu,

Wei,

et al. 2024

The FASEB Journal

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Recurrent spontaneous abortion (RSA) is a common pregnancy‐related disorder. Cbl proto‐oncogene like 1 (CBLL1) is an E3 ubiquitin ligase, which has been reported to vary with the menstrual cycle in the endometrium. However, whether CBLL1 is involved in the occurrence and development of RSA remains unclear. This study aimed to investigate the effects of CBLL1 on RSA. We analyzed the expression of CBLL1 in the decidua of RSA patients, as well as its functional effects on cellular senescence, oxidative stress, and proliferation of human endometrial stromal cells (HESCs). RNA sequencing was employed to identify a key downstream target gene regulated by CBLL1. We found that CBLL1 was upregulated in the decidua of RSA patients. Additionally, overexpression of CBLL1 promoted HESC senescence, increased oxidative stress levels, and inhibited proliferation. Phosphatase and tensin homolog located on chromosome 10 (PTEN) was identified as one of the important downstream target genes of CBLL1. In vivo experiments demonstrated that CBLL1 overexpression in the endometrium caused higher embryo absorption rate in mice. Consequently, elevated CBLL1 expression is a potential cause of RSA, representing a novel therapeutic target for RSA.

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“…Reasons for this imbalance can be manifold, including systemic immune alterations, genetic constitution, inflammatory effectors including immune disorders, stress, diet, physical exercises, and obesity, or altered activators including paternal factors, HLA matching, genetics of the embryo, and more. On a cellular basis, not only local immune cells but also trophoblast cells, as well as decidual epithelial and stromal cells, affect the balance by activating and inhibiting soluble and cell-to-cell-contact-mediated factors and receptors [ 24 , 42 , 51 , 52 , 97 , 98 , 99 , 100 ].…”

Section: Immune Implications In Adverse Pregnancy Outcomesmentioning

confidence: 99%

Immune Cell Functionality during Decidualization and Potential Clinical Application

Stope

Mustea

Sänger

et al. 2023

Life

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Due to a vast influx in the secretory phase of the menstrual cycle, leukocytes represent 40–50% of the decidua at the time of implantation. Their importance for the implantation, maintenance of pregnancy, and parturition are known yet not fully understood. Thus, in idiopathic infertility, decidual immune-related factors are speculated to be the cause. In this review, the immune cell functions in the decidua were summarized, and clinical diagnostics, as well as interventions, were discussed. There is a rising number of commercially available diagnostic tools. However, the intervention options are still limited and/or poorly studied. In order for us to make big steps towards the proper use of reproductive immunology findings, we need to understand the mechanisms and especially support translational research.

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Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions

Cited by 7 publications

References 29 publications

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion

Immune Cell Functionality during Decidualization and Potential Clinical Application

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