Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus

Ahamada, Mariame Mohamed; Jia, Yongsheng; Wu, Xiaochuan

doi:10.3389/fimmu.2021.734008

Cited by 52 publications

(30 citation statements)

References 133 publications

(149 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mtb can activate infected Mphs and thus change the cytokines and chemokine production. The ESAT-6 (early Secreted Antigenic Target 6 kDa) is thought to be one of the Mtb factors inducing the proinflammatory M1 phenotype at the start of the infection, which facilitates granuloma formation and then switches M polarization from M1 to M2 at a later stage of the infection [155].…”

Section: Macrophage Polarization Programsmentioning

confidence: 99%

Tuberculosis and Autoimmunity

2022

View full text Add to dashboard Cite

Tuberculosis remains a common and dangerous chronic bacterial infection worldwide. It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.

show abstract

Section: Macrophage Polarization Programsmentioning

confidence: 99%

Tuberculosis and Autoimmunity

2022

View full text Add to dashboard Cite

show abstract

“…The number of decidual effector Treg cells was reduced in patients with early miscarriage ( 64 ), and clonally expanded effector Treg cells were significantly reduced in patients with PE ( 65 ), as compared to normal pregnancies. Macrophages were classically polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in response to stimulation by different immune microenvironments ( 66 ). Studies ( 67 , 68 ) had shown that a decrease in the proportion of M2-like macrophages and an increase in total macrophages was detrimental to embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

et al. 2022

View full text Add to dashboard Cite

BackgroundEffectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE.MethodsThe GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis.ResultsWe identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01).ConclusionsOur preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

show abstract

“…These studies have demonstrated the role of macrophages in the pathogenesis of SLE. Additionally, experiments have increasingly reported a close relationship between SLE and macrophages [ 59 , 60 ]. Conversely, blocking macrophage activation alleviates the progression of SLE, suggesting that apoptotic double-stranded DNA-induced macrophage activation may play an important pathogenic role in the development of SLE [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

GBP2 acts as a member of the interferon signalling pathway in lupus nephritis

et al. 2022

View full text Add to dashboard Cite

Lupus nephritis (LN) is a common and serious clinical manifestation of systemic lupus erythematosus. However, the pathogenesis of LN is not fully understood. The currently available treatments do not cure the disease and appear to have a variety of side effects in the long term. The purpose of this study was to search for key molecules involved in the LN immune response through bioinformatics techniques to provide a reference for LN-specific targeted therapy. The GSE112943 dataset was downloaded from the Gene Expression Omnibus database, and 20 of the samples were selected for analysis. In total, 2330 differentially expressed genes were screened. These genes were intersected with a list of immune genes obtained from the IMMPORT immune database to obtain 128 differentially expressed immune-related genes. Enrichment analysis showed that most of these genes were enriched in the interferon signalling pathway. Gene set enrichment analysis revealed that the sample was significantly enriched for expression of the interferon signalling pathway. Further analysis of the core gene cluster showed that nine genes, GBP2, VCAM1, ADAR, IFITM1, BST2, MX2, IRF5, OAS1 and TRIM22, were involved in the interferon signalling pathway. According to our analysis, the guanylate binding protein 2 (GBP2), interferon regulatory factor 5 and 2′-5′-oligoadenylate synthetase 1 (OAS1) genes are involved in three interferon signalling pathways. At present, we do not know whether GBP2 is associated with LN. Therefore, this study focused on the relationship between GBP2 and LN pathogenesis. We speculate that GBP2 may play a role in the pathogenesis of LN as a member of the interferon signalling pathway. Further immunohistochemical results showed that the expression of GBP2 was increased in the renal tissues of LN patients compared with the control group, confirming this conjecture. In conclusion, GBP2 is a member of the interferon signalling pathway that may have implications for the pathogenesis of LN and serves as a potential biomarker for LN. Supplementary Information The online version contains supplementary material available at 10.1186/s12865-022-00520-5.

show abstract

Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus

Cited by 52 publications

References 133 publications

Tuberculosis and Autoimmunity

Tuberculosis and Autoimmunity

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

GBP2 acts as a member of the interferon signalling pathway in lupus nephritis

Contact Info

Product

Resources

About