B Cell ADAM10 Controls Murine Lupus Progression through Regulation of the ICOS:ICOS Ligand Axis

Lownik, Joseph C.; Wimberly, Jessica L.; Conrad, Daniel H.; Martin, Rebecca

doi:10.4049/jimmunol.1801207

Cited by 8 publications

(5 citation statements)

References 36 publications

(73 reference statements)

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“…Signaling Gα i nucleotide was positively correlated with ADAM10 maturation and activity on transitional B cells ( Hwang et al, 2018 ). Another study showed that ADAM10 is involved in murine lupus progression on B cells ( Lownik et al, 2019 ). Moreover, B cells are key predictors of successful treatment in patients with melanoma, in which mature and differentiated B cells are directly correlated with checkpoint inhibitor drugs ( Willsmore et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

Hermawan

Putri

2021

Saudi Pharmaceutical Journal

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Background Glioblastoma is one of the most aggressive and deadliest malignant tumors. Acquired resistance decreases the effectiveness of bevacizumab in glioblastoma treatment and thus increases the mortality rate in patients with glioblastoma. In this study, the potential targets of pentagamavunone-1 (PGV-1), a curcumin analog, were explored as a complementary treatment to bevacizumab in glioblastoma therapy. Methods Target prediction, data collection, and analysis were conducted using the similarity ensemble approach (SEA), SwissTargetPrediction, STRING DB, and Gene Expression Omnibus (GEO) datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using Webgestalt and DAVID, respectively. Hub genes were selected based on the highest degree scores using the CytoHubba. Analysis of genetic alterations and gene expression as well as Kaplan–Meier survival analysis of selected genes were conducted with cBioportal and GEPIA. Immune infiltration correlations between selected genes and immune cells were analyzed with database TIMER 2.0. Results We found 374 targets of PGV-1, 1139 differentially expressed genes (DEGs) from bevacizumab-resistant-glioblastoma cells. A Venn diagram analysis using these two sets of data resulted in 21 genes that were identified as potential targets of PGV-1 against bevacizumab resistance (PBR). PBR regulated the metabolism of xenobiotics by cytochrome P450. Seven potential therapeutic PBR, namely GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110 were found to have genetic alterations in 1.2%–30% of patients with glioblastoma. Analysis using the GEPIA database showed that the mRNA expression of ADAM10 , AKR1B1 , and HSD17B10 was significantly upregulated in glioblastoma patients. Kaplan–Meier survival analysis showed that only patients with low mRNA expression of AKR1B1 had significantly better overall survival than the patients in the high mRNA group. We also found a correlation between PBR and immune cells and thus revealed the potential of PGV-1 as an immunotherapeutic agent via targeting of PBR. Conclusion This study highlighted seven PBR, namely, GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110. This study also emphasized the potential of PBR as a target for immunotherapy with PGV-1. Further validation of the results of this study is required for the development of PGV-1 as an adjunct to immunotherapy for glioblastoma to counteract bevacizumab resistance.

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Section: Discussionmentioning

confidence: 99%

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

Hermawan

Putri

2021

Saudi Pharmaceutical Journal

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“…[28][29][30] ICOS and ICOSL can also be secreted as soluble formsnamely sICOS and sICOSLwhich may derive from alternative transcription of the gene, alternative splicing of the mRNA, or proteolytic cleavage of the membrane form. 31,32 Of note, the serum levels of sICOS and sICOSL are increased in some autoimmune diseases. [33][34][35][36][37] The aim of this study was to assess the expression of ICOS and ICOSL in plasma cell dyscrasias to investigate the role of this receptor system in malignant progression and end organ damages.…”

Section: Introductionmentioning

confidence: 99%

Inducible T‐cell co‐stimulator (ICOS) and ICOS ligand are novel players in the multiple‐myeloma microenvironment

et al. 2021

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The inducible T-cell co-stimulator (ICOS) is a T-cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B-cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte-bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie-Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL + MOPC-21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM.

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“…Tail DNA was prepared using the following procedure adapted from a previously described method [ 20 ]. Mice were genotyped using PCR QuantStudio 3 realtime PCR system (Thermo Fisher Scientific) with melt curve analysis.…”

Section: Methodsmentioning

confidence: 99%

Adipocyte ADAM17 plays a limited role in metabolic inflammation

et al. 2020

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The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global Adam17 knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using in vivo models. In this study, we developed an adipocyte-specific Adam17 knockout model using Adipoq-Cre-expressing mice crossed with Adam17-floxed mice. Using this model, we show that loss of adipocyte ADAM17 plays no evident role in baseline metabolic responses. Surprisingly, in a state of metabolic stress using high-fat diet (HFD), we observed that adipocyte ADAM17 had little effect overall on the metabolic phenotype as well as inflammatory cell populations. Using whole-body metabolic phenotyping, we show that loss of ADAM17 has no effect on energy utilization both at a baseline state as well as following HFD. However, lastly, using high-parameter flow cytometry, we show that loss of adipocyte ADAM17 alters macrophage and eosinophil populations following HFD. Overall, the studies presented here give more insight into the role of ADAM17 in metabolic responses and metabolic inflammation, specifically in adipocytes.

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B Cell ADAM10 Controls Murine Lupus Progression through Regulation of the ICOS:ICOS Ligand Axis

Cited by 8 publications

References 36 publications

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

Inducible T‐cell co‐stimulator (ICOS) and ICOS ligand are novel players in the multiple‐myeloma microenvironment

Adipocyte ADAM17 plays a limited role in metabolic inflammation

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