CD11b Activity Modulates Pathogenesis of Lupus Nephritis

Khan, Samia Q.; Khan, Imran; Gupta, Vineet

doi:10.3389/fmed.2018.00052

Cited by 76 publications

(72 citation statements)

References 70 publications

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“…ITGAM was identified as the top 1 hub gene and had the highest degree of connectivity. ITGAM encodes CD11b, a component of the macrophage-1 antigen complex (Mac1, also known as complement receptor 3 [CR3]), which together with CD18, form Mac-1 or CR3, a protein that mediates leukocyte adhesion, migration, and phagocytosis in different cells 50 - 53 . CD11b contributes to the phagocytosis of opsonized particles, including apoptotic cells and immune complex 53 .…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis

Qin

et al. 2020

Int. J. Med. Sci.

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Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM prognosis and advance potential therapeutic targets. Methods: The gene expression profile GSE109651 was obtained from Gene Expression Omnibus database, and then differentially expressed genes (DEGs) with P-value <0.05 and |log2 fold-change (FC)| > 2 were selected by the comparison of myeloma light-chain (LC) restricted SP (LC/SP) cells and MP CD138 + cells. Subsequently, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) network analysis were performed to identify the functional enrichment analysis of the DEGs and screen hub genes. Cox proportional hazards regression was used to select the potential prognostic DEGs in training dataset (GSE2658). The prognostic value of the potential prognostic genes was evaluated by Kaplan-Meier curve and validated in another external dataset (MMRF-CoMMpass cohort from TCGA). Results: Altogether, 403 up-regulated and 393 down-regulated DEGs were identified. GO analysis showed that the up-regulated DEGs were significantly enriched in innate immune response, inflammatory response, plasma membrane and integral component of membrane, while the down-regulated DEGs were mainly involved in protoporphyrinogen IX and heme biosynthetic process, hemoglobin complex and erythrocyte differentiation. KEGG pathway analysis suggested that the DEGs were significantly enriched in osteoclast differentiation, porphyrin and chlorophyll metabolism and cytokine-cytokine receptor interaction. The top 10 hub genes, identified by the plug-in cytoHubba of the Cytoscape software using maximal clique centrality (MCC) algorithm, were ITGAM, MMP9, ITGB2, FPR2, C3AR1, CXCL1, CYBB, LILRB2, HP and FCER1G. Modules and corresponding GO enrichment analysis indicated that myeloma LC/SP cells were significantly associated with immune system, immune response and cell cycle. The predictive value of the prognostic model including TFF3, EPDR1, MACROD1, ARHGEF12, AMMECR1, NFATC2, HES6, PLEK2 and SNCA was identified, and validated in another external dataset (MMRF-CoMMpass cohort from TCGA). Conclusions: In conclusion, this study provides reliable molecular biomarkers for screening, prognosis, as well as novel therapeutic targets for myeloma LC/SP cells.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis

Qin

et al. 2020

Int. J. Med. Sci.

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“…This demonstrates the immunomodulatory effect neutrophil CD11b expression exerts on the host response to infection. A persistent inflammatory response can be seen in autoimmunity and there is a higher prevalence in DS, recent studies suggest that reduced CD11b is associated with chronic inflammation in SLE and lupus nephritis [ 40 , 41 ]. Neutrophil CD11b is also decreased in septic shock and correlated with poorer outcomes [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Altered endotoxin responsiveness in healthy children with Down syndrome

et al. 2018

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BackgroundDown syndrome (DS) is the most common syndromic immunodeficiency with an increased risk of infection, mortality from sepsis, and autoinflammation. Innate immune function is altered in DS and therefore we examined responses in CD11b and Toll like receptor 4 (TLR-4), which are important immune cell surface markers upregulated in response to Lipopolysaccharide (LPS) endotoxin, and the immunomodulator melatonin. Neutrophil and monocyte responses to LPS and melatonin in children with Down syndrome (DS) who were clinically stable were compared to age-matched controls. Whole blood was incubated with LPS and melatonin and the relative expression of CD11b and TLR-4 evaluated by flow cytometry.ResultsChildren with DS had an increased response to LPS in neutrophils and intermediate monocytes, while also having elevated TLR-4 expression on non-classical monocytes compared to controls at baseline. Melatonin reduced CD11b expression on neutrophils, total monocytes, both classical and intermediate sub-types, in children with DS and controls.ConclusionMelatonin could represent a useful clinical adjunct in the treatment of sepsis as an immunomodulator. Children with DS had increased LPS responses which may contribute to the more adverse outcomes seen in sepsis.

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“…NK cells pre-treated with LA-1 displayed less STAT5 phosphorylation in response to IL-12, and consequently reduced secretion of TNF-α and IFN-γ [130]. LA-1 has been successfully used to prevent inflammation in hypoxia-induced lung injury in rats [345] and in an autoimmune nephritis mouse model [346,347]. Since myeloid cells express both LFA-1 and MAC-1 that bind other (immune) cells via ICAM, specific blockade of either β2 integrin may be compensated by the other.…”

Section: β2 Integrins As Therapeutic Targetsmentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

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β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.

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CD11b Activity Modulates Pathogenesis of Lupus Nephritis

Cited by 76 publications

References 70 publications

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis

Altered endotoxin responsiveness in healthy children with Down syndrome

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

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