GPNMB plays an active role in the M1/M2 balance

Zhang, Hengfang; Zhang, Shuang; Dang, Xuan; Lin, Lexun; Ren, Liping; Song, Rong

doi:10.1016/j.tice.2021.101683

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…The origin of HM EVs may explain the functional effects seen prior studies, especially when inflammatory regulation was examined (Zonneveld et al., 2021 ). In our transcriptomic data, preterm mRNA was most significantly upregulated for gene signatures of GPNMB+ macrophages, generally attributed to M2 macrophages and an anti‐inflammatory phenotype (Zhang et al., 2022 ; Zhou et al., 2017 ). Given the vulnerability of infants, especially premature infants, to gut inflammatory diseases such as necrotising enterocolitis, the EV cargo may provide significant protection.…”

Section: Discussionmentioning

confidence: 67%

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Vahkal,

Altosaar,

Tremblay

et al. 2023

J of Extracellular Bio

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Human milk extracellular vesicles (HM EVs) are proposed to protect against disease development in infants. This protection could in part be facilitated by the bioactive EV cargo of proteins and RNA. Notably, mothers birth infants of different gestational ages with unique needs, wherein the EV cargo of HM may diverge. We collected HM from lactating mothers within two weeks of a term or preterm birth. Following purification of EVs, proteins and mRNA were extracted for proteomics and sequencing analyses, respectively. Over 2000 protein groups were identified, and over 8000 genes were quantified. The total number of proteins and mRNA did not differ significantly between the two conditions, while functional bioinformatics of differentially expressed cargo indicated enrichment in immunoregulatory cargo for preterm HM EVs. In term HM EVs, significantly upregulated cargo was enriched in metabolism‐related functions. Based on gene expression signatures from HM‐contained single cell sequencing data, we proposed that a larger portion of preterm HM EVs are secreted by immune cells, whereas term HM EVs contain more signatures of lactocyte epithelial cells. Proposed differences in EV cargo could indicate variation in mother's milk based on infants’ gestational age and provide basis for further functional characterisation.

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Section: Discussionmentioning

confidence: 67%

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Vahkal,

Altosaar,

Tremblay

et al. 2023

J of Extracellular Bio

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“…Furthermore, knock-down of GPNMB in mouse bone marrow-derived macrophages reduced the secretion of the anti-inflammatory cytokines IL-10 and TGF-β, while the secretion of proinflammatory cytokines IL-1β and TNF-α was increased [ 49 ]. Accordingly, overexpression of GPNMB in macrophages promoted the secretion of anti-inflammatory and inhibited the secretion of pro-inflammatory factors [ 50 ]. This “innate” regulatory mechanism could explain two observations we made in this study: (1) Increased infiltration of TAMs in the core of KO.…”

Section: Discussionmentioning

confidence: 99%

Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma

Yalcin,

Haneke,

Efe

et al. 2024

acta neuropathol commun

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Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment. The impact of host-derived GPNMB on tumor growth was confirmed in two distinct murine glioma cell lines in organotypic brain slices from GPNMB-KO and control mice. Using published data bases of human glioma, the elevated levels in TAMs could be confirmed and the GPNMB expression correlated with a poorer survival.

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“…Marker genes of the maternal PAMM subcluster included APOE, APOC1, VIM, LGALS1, and GPNMB among others, an expression pattern consistent with previously reported maternal placental macrophage transcriptional profiles (39,40). High expression of LGALS1/3 and GPNMB by the PAMM cluster suggests a role in inflammation regulation (41)(42)(43), which was echoed by GO analyses identifying enrichment in immune response and immunomodulatory pathways (e.g. "antigen processing and presentation, "positive regulation of cytokine production", and "regulation of innate immune response") .…”

Section: Hofbauer Cells Are a Heterogeneous Population With Subcluste...mentioning

confidence: 97%

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

Shook,

Batorsky,

De Guzman

et al. 2023

Preprint

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The SARS-CoV-2 virus activates maternal and placental immune responses, which in the setting of other infections occurring during pregnancy are known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. Here, we assessed the impact of maternal SARS-CoV-2 on HBCs isolated from term placentas using single-cell RNA-sequencing. We demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells, with altered morphology and impaired synaptic pruning behavior compared to HBC models from negative controls. These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.

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GPNMB plays an active role in the M1/M2 balance

Cited by 12 publications

References 24 publications

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

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