CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Zhang, Bin; Zhang, Yuan; Xiong, Lei; Li, Yuzhe; Zhang, Yunliang; Jiang, Hui; Li, Can; Liu, Yunqi; Liu, Xindong; Liu, Haofei; Ping, Yi‐Fang; Zhang, Qiangfeng Cliff; Zhang, Zheng; Bian, Xiu‐Wu; Zhao, Yan; Hu, Xiaoyu

doi:10.1084/jem.20211191

Cited by 42 publications

(29 citation statements)

References 55 publications

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“…Moreover, despite the fact that the literature reports a reduction of non-classical monocytes in COVID-19 patients ( 68 ), in our dataset the only subpopulation altered in frequency was the one of cMo cytotoxic monocytes, which increased in severe and moderate patients. Finally, our data showing the expression of IL-7R in cytotoxic monocytes are consistent with the presence of IL7R + monocytes/macrophages in COVID-19 BALF ( 69 ), and further support the hypothesis that these cells are key players in the progress of the disease.…”

Section: Discussionsupporting

confidence: 85%

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

et al. 2022

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Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic gene sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of human leukocyte antigen (HLA) genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. A machine learning approach was developed and applied to two single-cell transcriptome public datasets, from gastrointestinal cancer and Coronavirus disease 2019 (COVID-19) patients. The dissection of these datasets through our classification revealed that patients with advanced cancers showed a selective increase in monocytes enriched in platelet-related pathways. Of note, the signature associated with this population correlated with worse prognosis in gastric cancer patients. Conversely, after immunotherapy, the most activated population was composed of interferon-related monocytes, consistent with an upregulation in interferon-related genes in responder patients compared to non-responders. In COVID-19 patients we confirmed a global activated phenotype of the entire monocyte compartment, but our classification revealed that only cytotoxic monocytes are expanded during the disease progression. Collectively, this study unravels an unexpected complexity among human circulating monocytes and highlights the existence of specialized populations differently engaged depending on the pathological context.

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Section: Discussionsupporting

confidence: 85%

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

et al. 2022

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“…Monocytes belong to the monocyte-phagocytic system ( 33 ). Monocytes are the first line of host defense, which are a key mediator of acute and chronic inflammation ( 34 ), and can induce immune-inflammatory responses ( 35 ). HDL-c has anti-inflammatory properties and may be essential for the prevention of other inflammatory diseases ( 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance of novel inflammatory biomarkers based on ratios of laboratory indicators for nonalcoholic fatty liver disease

Zhao

Xia

et al. 2022

Front. Endocrinol.

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IntroductionThere is few effective biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD) in clinical practice. This study was aimed to investigate the predictive ability of novel inflammatory biomarkers, including the monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), for NAFLD.MethodsA total of 4465 outpatients diagnosed with NAFLD and 3683 healthy controls were enrolled between May 2016 and November 2021 from the West China Hospital of Sichuan University, and anthropometric and laboratory examination data were collected. The two-sample Mann-Whitney U test and binary logistic regression analysis were used to evaluate the correlations between four inflammatory biomarkers and NAFLD. The areas under the curves (AUCs) of receiver operating characteristic were used to evaluate their predictive ability for NAFLD.ResultsThe MHR, NLR and LMR were higher in patients with NAFLD than in healthy controls (P<0.001), whereas the PLR was remarkably lower (P<0.001). The OR values of the MHR, NLR, PLR, and LMR were 1.599 (1.543-1.658), 1.250 (1.186-1.317), 0.987(0.986-0.988) and 1.111(1.083-1.139), respectively(P<0.001). After adjusting for confounding factors, MHR was still the most relevant risk factor for NAFLD compared with other inflammatory markers (P<0.001). The AUCs of the MHR, NLR, PLR, and LMR were as follows: 0.663 (0.651-0.675), 0.524 (0.512-0.537), 0.329 (0.318-0.341), and 0.543 (0.530-0.555), respectively (P<0.001). Furthermore, the diagnostic model combining the MHR with alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, fasting blood glucose, creatinine, uric acid, and body mass index had the best AUC of 0.931 (0.925-0.936).ConclusionsMHR was superior to NLR, PLR and LMR as an inflammatory biomarker in the prediction of NAFLD. When combined with relevant laboratory parameters, the MHR may improve the clinical noninvasive diagnosis of NAFLD.

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“…The NKG2D receptor was also a new potential target to regulate the direct interaction between SARS-CoV-2 and NK cells and could be used as a therapeutic target for COVID-19 ( 11 ). Single-cell transcriptome analyzes of human inflammatory monocytes from COVID-19 and RA patients showed that a group of CD127 (IL-7 receptor subunit) positive cells induced initially inactive monocytes to respond to IL-7 and negatively affected the inflammatory phenotype of monocytes ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and System Biology Approach to Identify the Influences of COVID-19 on Rheumatoid Arthritis

Tang

Zhang

et al. 2022

Front. Immunol.

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BackgroundSevere coronavirus disease 2019 (COVID -19) has led to a rapid increase in mortality worldwide. Rheumatoid arthritis (RA) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the molecular mechanisms underlying RA and CVOID-19 are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19 and RA using bioinformatics and a systems biology approach.MethodsTwo Differentially expressed genes (DEGs) sets extracted from GSE171110 and GSE1775544 datasets were intersected to generate common DEGs, which were used for functional enrichment, pathway analysis, and candidate drugs analysis.ResultsA total of 103 common DEGs were identified in the two datasets between RA and COVID-19. A protein-protein interaction (PPI) was constructed using various combinatorial statistical methods and bioinformatics tools. Subsequently, hub genes and essential modules were identified from the PPI network. In addition, we performed functional analysis and pathway analysis under ontological conditions and found that there was common association between RA and progression of COVID-19 infection. Finally, transcription factor-gene interactions, protein-drug interactions, and DEGs-miRNAs coregulatory networks with common DEGs were also identified in the datasets.ConclusionWe successfully identified the top 10 hub genes that could serve as novel targeted therapy for COVID-19 and screened out some potential drugs useful for COVID-19 patients with RA.

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CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Cited by 42 publications

References 55 publications

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

Diagnostic performance of novel inflammatory biomarkers based on ratios of laboratory indicators for nonalcoholic fatty liver disease

Bioinformatics and System Biology Approach to Identify the Influences of COVID-19 on Rheumatoid Arthritis

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