Leukocyte immunoglobulin-like receptor subfamily B: A novel immune checkpoint molecule at the maternal-fetal interface

Wang, Jing; Zhao, Sijia; Wang, Liling; Lin, Xinxiu; Mor, Gil; Liao, Aihua

doi:10.1016/j.jri.2022.103764

Cited by 4 publications

(6 citation statements)

References 117 publications

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“…Unsurprisingly, the RAD51D network includes its paralogs RAD51B, RAD51C, XRCC2M and XRCC3, as well as SFR1, all of which are involved in DNA and double strand sequence repair (38, 39) ( 6G ). FCGR2B had a wide network of interactions including LILRB2, part of the LILR family of receptors, which are known to play a role in immune response and tolerance and have been implicated in developmental processes of pregnancy ( 6H) (40) as well as height (32). RPN1 and RPN2 are glycoproteins, and associated with other proteins involved in glycosylation, including DAD1, STT3A, STT3B, MAGT1 and DDOST ( 6I ).…”

Section: Resultsmentioning

confidence: 99%

Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis

McBride,

Fernández-Sanlés,

Arab

et al. 2023

Preprint

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Fetal growth is an indicator of fetal survival, regulated by maternal and fetal influences, but little is known about the underlying molecular mechanisms. We used Mendelian randomization to explore the effects of maternal and fetal genetically-instrumented plasma proteins on birth weight using genome-wide association summary data (n=406,063 with maternal and/or fetal genotype), with independent replication (n=74,932 mothers and n=62,108 offspring), and colocalisation. Higher genetically-predicted maternal levels of PCSK1 increased birthweight (mean-difference: 9g (95% CI: 5g, 13g) per 1 standard deviation protein level). Higher maternal levels of LGALS4 decreased birthweight (-54g (-29g, -80g)), as did VCAM1, RAD51D and GP1BA. In the offspring, higher genetically-predicted fetal levels of LGALS4 (46g (23g, 70g)) increased birthweight, alongside FCGR2B. Higher offspring levels of PCSK1 decreased birth weight (-9g (-16g, 4g), alongside LEPR. Results support maternal and fetal protein effects on birth weight, implicating roles for glucose metabolism, energy homeostasis, endothelial function and adipocyte differentiation.

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Section: Resultsmentioning

confidence: 99%

Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis

McBride,

Fernández-Sanlés,

Arab

et al. 2023

Preprint

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“…Additionally, LILRB1 binds to various pathogens, including, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), opsonised dengue virus, cytomegalovirus (CMV), calcium-binding proteins S100A8 and A9 and repetitive interspersed family of polypeptides (RIFIN) (9, 19,23,[94][95][96][97][98]. LILRB2 binds to ANGPTLs (similar to LILRB3 and LILRB5), HLA I-like proteins, Nogo66, complement split products (CSP), oligomeric b-amyloid, UL18, RTN4, MAG, OMgp, RIFIN and SEMA4A in activated CD4 + T cells (11,14,19,41,92,(146)(147)(148)(149). LILRB3 is the least studied LILRB and its natural ligands have not been fully elucidated.…”

Section: Lilr Ligandsmentioning

confidence: 99%

“…LILRB3 is the least studied LILRB and its natural ligands have not been fully elucidated. Although, regarded as an orphan receptor, recent findings suggest that LILRB3 interacts with ANGPTL2 and 5, complement components, and cytokeratin-associated proteins exposed on necrotic tumour cells and bacteria such as S. aureus (6,23,89,92,98,146,148). Hence, LILRB3 engagement by ligands expressed on necrotic cancer cells or pathogens may subvert immune responses.…”

Section: Lilr Ligandsmentioning

confidence: 99%

“…Recently, apolipoprotein (APOE) 4 was reported as a putative LILRB3 ligand, which is recognised by the D2/D4 regions LILRB3 (175). LILRB4 has been described to bind to APOE (185), ALCAM/ CD166 (186), galectin-8 (188), CNTFR (23,41,92) and fibronectin (93, 187), while LILRB5 binds to ANGPTLs, HLA-B7 and HLA-B27 heavy chains and Bacillus Calmette-Gueŕin (146,204).…”

Section: Lilr Ligandsmentioning

confidence: 99%

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Human leukocyte immunoglobulin-like receptors in health and disease

Redondo-García,

Barritt,

Papagregoriou

et al. 2023

Front. Immunol.

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Human leukocyte immunoglobulin (Ig)-like receptors (LILR) are a family of 11 innate immunomodulatory receptors, primarily expressed on lymphoid and myeloid cells. LILRs are either activating (LILRA) or inhibitory (LILRB) depending on their associated signalling domains (D). With the exception of the soluble LILRA3, LILRAs mediate immune activation, while LILRB1-5 primarily inhibit immune responses and mediate tolerance. Abnormal expression and function of LILRs is associated with a range of pathologies, including immune insufficiency (infection and malignancy) and overt immune responses (autoimmunity and alloresponses), suggesting LILRs may be excellent candidates for targeted immunotherapies. This review will discuss the biology and clinical relevance of this extensive family of immune receptors and will summarise the recent developments in targeting LILRs in disease settings, such as cancer, with an update on the clinical trials investigating the therapeutic targeting of these receptors.

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“…These antigen fragments are then presented to T cells through major histocompatibility complex (MHC) molecules (MHC-I molecules present endogenous antigens to CD8+ T cells, while MHC-II molecules present exogenous antigens to CD4+ T cells) (154, 155). Simultaneously, uDCs express co-stimulatory molecules such as CD80 and CD86, which interact with relevant receptors on the surface of T cells (such as CD28), providing a second signal that promotes T cell activation and proliferation (156). uDCs can also express immune regulatory molecules such as PD-L1.…”

Section: Other Immune Cells In Embryo Implantation and Developmentmentioning

confidence: 99%

Roles of immune microenvironment in the female reproductive maintenance and regulation: novel insights into the crosstalk of immune cells

Dai,

Xu,

Gong

et al. 2023

Front. Immunol.

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Female fertility decline is an accumulative consequence caused by complex factors, among them, the disruption of the immune profile in female reproduction stands out as a crucial contributor. Presently, the effects of immune microenvironment (IME) on the female reproductive process have attracted increasing attentions for their dynamic but precisive roles. Immunocytes including macrophages, dendritic cells, T cells, B cells and neutrophils, with diverse subpopulations as well as high plasticity functioned dynamically in the process of female reproduction through indirect intercellular communication via specific cytokine release transduced by molecular signal networks or direct cell-cell contact to maintain the stability of the reproductive process have been unveiled. The immune profile of female reproduction in each stage has also been meticulously unveiled. Especially, the application of single-cell sequencing (scRNA-seq) technology in this process reveals the distribution map of immune cells, which gives a novel insight for the homeostasis of IME and provides a research direction for better exploring the role of immune cells in female reproduction. Here, we provide an all-encompassing overview of the latest advancements in immune modulation within the context of the female reproductive process. Our approach involves structuring our summary in accordance with the physiological sequence encompassing gonadogenesis, folliculogenesis within the ovaries, ovulation through the fallopian tubes, and the subsequent stages of embryo implantation and development within the uterus. Our overarching objective is to construct a comprehensive portrayal of the immune microenvironment (IME), thereby accentuating the pivotal role played by immune cells in governing the intricate female reproductive journey. Additionally, we emphasize the pressing need for heightened attention directed towards strategies that focus on immune interventions within the female reproductive process, with the ultimate aim of enhancing female fertility.

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Leukocyte immunoglobulin-like receptor subfamily B: A novel immune checkpoint molecule at the maternal-fetal interface

Cited by 4 publications

References 117 publications

Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis

Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis

Human leukocyte immunoglobulin-like receptors in health and disease

Roles of immune microenvironment in the female reproductive maintenance and regulation: novel insights into the crosstalk of immune cells

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