NK cells and other innate lymphoid cells at the maternal-fetal interface

AbstractInnate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here we describeToxoplasma gondiiinfection converts NK cells into cells resembling steady-state ILC1s that are heterogeneous and distinct from both steady-state NK cells and ILC1s in uninfected mice. Most toxoplasma-induced ILC1s were Eomes-dependent, indicating that NK cells can give rise to Eomes−Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

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Innate lymphoid cells at the maternal-fetal interface: Implications in preterm labor

10.21203/rs.2.11586/v1 ◽

2019 ◽

Author(s):

João Fernando Pereira Mendes ◽

Paulo Rodrigues Santos ◽

Ana Areia ◽

Jani Sofia Almeida ◽

Vera Alves ◽

...

Keyword(s):

Preterm Labor ◽

Group Analysis ◽

Neonatal Morbidity ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Data Set ◽

Proinflammatory Mediators ◽

Maternal Peripheral Blood ◽

Human Labor ◽

Maternal Fetal Interface

Abstract Background: Preterm labor (PTL) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The aim of this work was to analyze the abilities of innate lymphoid cells (ILCs), specifically ILC3 NCR- cells, to act as proinflammatory mediators and to elucidate their role in pregnancy. Accordingly, we hypothesize that altered ILC numbers may prompt preterm labor (PTL). Methods: We analyzed thirteen full term labor (FTL) and seven PTL pregnant women for the presence of ILCs. ILCs were isolated and characterized from maternal peripheral blood, maternal-fetal interface, and cord blood samples, using flow cytometry. For group analysis, two-way ANOVA was performed. Each data set was analyzed using student t-test with a confidence interval of 95%. Results: A tendency for decreased ILCs numbers in PTL samples compared to those in FTL samples was observed. Additionally, ILC3 NCR- cells were significantly increased in both PTL and FTL groups, when compared to ILC3NCR+. Conclusion: Our results support a potential inflammatory role of ILC3 NCR- in the instigation of labor. Moreover our work highlights the importance of ILCs actions in the regulation of labor.

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Molecular definition of group 1 innate lymphoid cells in the mouse uterus

10.1101/330068 ◽

2018 ◽

Author(s):

Iva Filipovic ◽

Laura Chiossone ◽

Paola Vacca ◽

Russell S Hamilton ◽

Tiziano Ingegnere ◽

...

Keyword(s):

Nk Cells ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Memory Cells ◽

Mouse Uterus ◽

Protein Ubiquitination ◽

Reproductive Life ◽

Definition Of ◽

Molecular Patterns ◽

Group 1

ABSTRACTDetermining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.

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Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

10.1101/2020.07.17.206433 ◽

2020 ◽

Author(s):

Laura Ducimetière ◽

Giulia Lucchiari ◽

Gioana Litscher ◽

Marc Nater ◽

Laura Heeb ◽

...

Keyword(s):

Liver Metastasis ◽

Nk Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Great Promise ◽

Type I ◽

Metastatic Niche

SUMMARYThe liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and non-redundant action of two innate lymphocyte subpopulations, conventional NK cells (cNKs) and tissue-resident type I Innate Lymphoid Cells (trILC1s), is essential for anti-metastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 control metastatic seeding, whereas cNKs restrain outgrowth. The antimetastatic activity of cNKs is regulated in a tumor type-specific fashion. Thereby, individual cancer cell lines orchestrate the emergence of cNK subsets with unique phenotypic and functional traits. Understanding cancer-cell- as well as innate-cell-intrinsic factors will allow the exploitation of hepatic innate cells for development of novel cancer therapies.SignificanceInnate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires the collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche inducing specific changes in cNKs and trILC1s. Further, we uncover specific cNK subsets that can be manipulated to improve their anti-metastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes.HighlightscNKs and trILC1s collaborate to control hepatic metastasistrILC1s restrict seeding and cNKs control outgrowth of cancer cells in the liverIndividual cancer cell lines orchestrate a distinct metastatic nicheThe metastatic niche dictates the phenotype and function of cNKs

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Innate Lymphoid Cells in Human Pregnancy

Frontiers in Immunology ◽

10.3389/fimmu.2020.551707 ◽

2020 ◽

Vol 11 ◽

Author(s):

João Mendes ◽

Ana Luísa Areia ◽

Paulo Rodrigues-Santos ◽

Manuel Santos-Rosa ◽

Anabela Mota-Pinto

Keyword(s):

Nk Cells ◽

Innate Lymphoid Cells ◽

Adverse Outcomes ◽

Lymphoid Cells ◽

Perinatal Medicine ◽

Effector Cells ◽

Human Pregnancy ◽

Group 3 ◽

Group 2 ◽

In Pregnancy

Innate lymphoid cells (ILCs) are a new set of cells considered to be a part of the innate immune system. ILCs are classified into five subsets (according to their transcription factors and cytokine profile) as natural killer cells (NK cells), group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Functionally, these cells resemble the T helper population but lack the expression of recombinant genes, which is essential for the formation of T cell receptors. In this work, the authors address the distinction between peripheral and decidual NK cells, highlighting their diversity in ILC biology and its relevance to human pregnancy. ILCs are effector cells that are important in promoting immunity, inflammation, and tissue repair. Recent studies have directed their attention to ILC actions in pregnancy. Dysregulation or expansion of pro-inflammatory ILC populations as well as abnormal tolerogenic responses may directly interfere with pregnancy, ultimately resulting in pregnancy loss or adverse outcomes. In this review, we characterize these cells, considering recent findings and addressing knowledge gaps in perinatal medicine in the context of ILC biology. Moreover, we discuss the relevance of these cells not only to the process of immune tolerance, but also in disease.

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The Role of NK Cells and Innate Lymphoid Cells in Brain Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2020.01549 ◽

2020 ◽

Vol 11 ◽

Author(s):

Alexander James Sedgwick ◽

Nazanin Ghazanfari ◽

Patrick Constantinescu ◽

Theo Mantamadiotis ◽

Alexander David Barrow

Keyword(s):

Nk Cells ◽

Brain Cancer ◽

Innate Lymphoid Cells ◽

Lymphoid Cells

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