CD31+, CD38+, CD44+, and CD103+ lymphocytes in peripheral blood, bronchoalveolar lavage fluid and lung biopsy tissue in sarcoid patients and controls

Aleksonienė, Regina; Besusparis, Justinas; Gruslys, Vygantas; Jurgauskienė, Laimutė; Laurinavičienė, Aida; Laurinavičius, Arvydas; Malickaitė, Radvilė; Norkūnienė, Jolita; Zablockis, Rolandas; Žurauskas, Edvardas; Danila, Edvardas

doi:10.21037/jtd-20-2396

Cited by 7 publications

(18 citation statements)

References 56 publications

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“…A feature of sarcoidosis is the accumulation of CD4 + T lymphocytes in the granulomas [ 19 ]. As expected, CD4 + T cell percentages were lower in peripheral blood than in lymph nodes [ 12 ]. The role of CD4 + T cells in the immunopathogenesis of sarcoidosis is well established [ 19 , 20 ], whereas less is known about cytotoxic CD8 + T cells.…”

Section: Discussionsupporting

confidence: 74%

“…Integrins could also mediate lymphocyte homing and migration into tissues [ 9 , 24 ]. Thus, there is still great interest in cellular biomarkers that could be related to inflammation and immune cell migration [ 12 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…This molecule can promote T-cell migration into the epithelium and is involved in retaining lymphocytes in the mucosa [ 11 ]. The literature on sarcoidosis reports CD103 to be stage-dependent, and mainly related to stages II and III [ 12 ]. CD103 is certainly expressed on 95% of intraepithelial CD4 + lymphocytes in the mucosa, but on less than 2% of circulating peripheral blood lymphocytes [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

d’Alessandro

Gangi

Cavallaro

et al. 2022

Life

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(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution and compartmentalisation of CD103 expression on T cell subsets in BAL, peripheral blood mononuclear cells (PBMC) and lymph nodes (LLN) from sarcoidosis patients. (2) Patients: We consecutively and prospectively enrolled 14 sarcoidosis patients. We collected PBMC, LLN and BAL at the same time from all patients. Through flow cytometric analysis, we analysed the expression of CD103 on regulatory and follicular T cell subsets. (3) Results: All patients were in radiological Scadding stage II. The multivariate analysis found that the variables which most influenced the peripheral blood compartment were high CD8+ and low ThReg, CD8+CD103+ and Tfh cell percentages. A principal component analysis plot performed to distinguish LLN, BAL and PBMC showed that they separated on the basis of CD4+, CD4+CD103+, CD8+, CD8+CD103+, TcEffector, TcNaive, ThNaive, ThEffector, Threg, ThregCD103+, Tfh, TcfCXC5+ and CD4+CD103+/CD4+ with 65.96% of the total variance. (4) Conclusions: Our study is the first to report a link between the imbalance in circulating, alveolar and lymph node CD8+ and CD8+CD103+ T cells, ThReg, Tfh and ThNaive and the CD103+CD4+/CD4+ T cell ratio in the development of sarcoidosis. These findings shine a spotlight on the pathogenesis of sarcoidosis and may offer new predictors for diagnosis. Our study provides additional understanding for a personalised, and hopefully more effective treatment of sarcoidosis.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

d’Alessandro

Gangi

Cavallaro

et al. 2022

Life

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“…Multifunctional membrane surface glycoprotein ( CD38 ) is considered as a marker of immune activation and involved in the regulation of lymphocyte adhesion to endothelial cells. Both CD3 + CD4 + CD38 + and CD38+ B cell subsets were found to be elevated in BAL as markers of an acute immune response in sarcoidosis patients ( 27 , 28 ). In addition to lymphocytes, PSTPIP2 , a gene supposed to be associated with autoinflammatory processes of macrophages in a mouse model, was found to be upregulated in progressive fibrotic pulmonary sarcoidosis ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

A transcriptomics-based meta-analysis identifies a cross-tissue signature for sarcoidosis

Jiang

Jiang²,

Costabel³

et al. 2022

Front. Med.

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Sarcoidosis is a granulomatous disease of unknown etiology, immunologically characterized by a Th1 immune response. Transcriptome-wide expression studies in various types of sarcoid tissues contributed to better understanding of disease mechanisms. We performed a systematic database search on Gene Expression Omnibus (GEO) and utilized transcriptomic data from blood and sarcoidosis-affected tissues in a meta-analysis to identify a cross-tissue, cross-platform signature. Datasets were further separated into training and testing sets for development of a diagnostic classifier for sarcoidosis. A total of 690 differentially expressed genes were identified in the analysis among various tissues. 29 of the genes were robustly associated with sarcoidosis in the meta-analysis both in blood and in lung-associated tissues. Top genes included LINC01278 (P = 3.11 × 10–13), GBP5 (P = 5.56 × 10–07), and PSMB9 (P = 1.11 × 10–06). Pathway enrichment analysis revealed activated IFN-γ, IL-1, and IL-18, autophagy, and viral infection response. IL-17 was observed to be enriched in peripheral blood specific signature genes. A 16-gene classifier achieved excellent performance in the independent validation data (AUC 0.711–0.964). This study provides a cross-tissue meta-analysis for expression profiles of sarcoidosis and identifies a diagnostic classifier that potentially can complement more invasive procedures.

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“…While these associations are novel, multiple target genes of these miRNAs have been implicated in sarcoidosis previously, including the genes AKT1, CD44, JAG1 , and PTGS2 . For example, CD44 has been found in areas of granuloma formation and fibrosis 28 and is differentially expressed between Lofgren syndrome versus non-Lofgren syndrome subjects 29 . Through integrating genes with evidence of both DE and DM, we identified biologically relevant genes in sarcoidosis versus controls, including HIF1A and TGFB1 .…”

Section: Discussionmentioning

confidence: 99%

Multi-Omic Signatures of Sarcoidosis and Progression in Bronchoalveolar Lavage Cells

Konigsberg

Lin

Liao

et al. 2023

Preprint

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Introduction: Sarcoidosis is a heterogeneous, granulomatous disease that can prove difficult to diagnose, with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential genomic biomarkers. Methods: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of diagnosis and phenotype, adjusting for age, sex, and smoking. We built a supervised multi-omics model using a subset of features from each dataset. Results: We identified 46,812 CpGs, 1,842 mRNAs, and 5 miRNAs associated with sarcoidosis versus controls and 1 mRNA, SEPP1 - a protein that supplies selenium to cells, associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway in sarcoidosis, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. Conclusions: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing will be required for confirmation.

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CD31+, CD38+, CD44+, and CD103+ lymphocytes in peripheral blood, bronchoalveolar lavage fluid and lung biopsy tissue in sarcoid patients and controls

Cited by 7 publications

References 56 publications

CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

A transcriptomics-based meta-analysis identifies a cross-tissue signature for sarcoidosis

Multi-Omic Signatures of Sarcoidosis and Progression in Bronchoalveolar Lavage Cells

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