CD49d-Treg Cells with High Suppressive Capacity are Remarkably Less Efficient on Activated CD45RA-than on Naive CD45RA+Teff Cells

Kraczyk, Britta; Remus, Ralph; Hardt, Cornelia

doi:10.1159/000363004

Cited by 19 publications

(20 citation statements)

References 31 publications

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“…The alpha chain of α4β1 integrin is encoded by ITGA4 (CD49d) gene. The ability of CD49d + Tregs to suppress effector T cells was found to be weaker compared to CD49d negative T cells in vitro 76 . In our study, CD49d expression was increased in PD and also PD patients displayed higher frequencies of CD49d + Tregs in the peripheral blood.…”

Section: Discussionmentioning

confidence: 88%

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Karaaslan

Kahraman

Şanlı

et al. 2021

Sci Rep

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Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein–protein interaction analyses were performed with STRING. Expression levels of randomly selected DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in PBMC. A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the effort of the immune system to suppress ongoing neuroinflammation.

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Section: Discussionmentioning

confidence: 88%

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Karaaslan

Kahraman

Şanlı

et al. 2021

Sci Rep

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“…Allergic asthma makes up most asthma cases, characterized by activation of type-2 T helper cells, IgE production, eosinophilia, and an inappropriate T cell response to environmental allergens [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

Ding

Zhang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Regulatory T cells (Treg) are critical regulators of asthma. Crocetin is isolated from Chinese herb saffron and is a natural carotenoid dicarboxylic acid with anti-inflammatory potential. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied. Methods: We used Crocetin to treat mice with established ovalbumin (OVA)-induced asthma. We purified CD4+CD25+ Treg cells by flow cytometry and analyzed the levels of two immunoregulatory proteins Foxp3 and tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in Treg cells. We depleted either Foxp3 or TIPE2 in mouse lung through lentivirus-mediated delivery of shRNA, and analyzed their effects on severity of asthma and Treg cells after Crocetin treatment. Results: Crocetin treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice. Moreover, Crocetin significantly increased the levels of TIPE2 and Foxp3 in Treg cells and the number of Treg cells. Depletion of Foxp3 abolished the increased in Treg cells, and the effects of Crocetin on the severity of asthma, without affecting TIPE2 levels in Treg cells. On the other hand, depletion of TIPE2 abolished both the increased in Treg cells and the effects of Crocetin on the severity of asthma, through suppressing Foxp3. Conclusion: Crocetin may activate Foxp3 through TIPE2 in asthma-associated Treg cells to mitigate the severity of asthma.

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“…The alpha chain of α4β1 integrin is encoded by ITGA4 (CD49d) gene. The ability of CD49d+ Tregs to suppress effector T cells was found to be weaker compared to CD49d negative T cells in vitro (59). In our study, CD49d expression was increased in PD and also PD patients displayed higher frequencies of CD49d + Tregs in the peripheral blood.…”

Section: Flow Cytometry Analysesmentioning

confidence: 41%

Identification of Molecular Mechanisms in Parkinson’s Disease Pathogenesis: Significance of Survival and Inflammation Pathways

Karaaslan

Kahraman

Şanlı

et al. 2020

Preprint

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Background: Our aim was to identify the differentially expressed genes (DEGs) between Parkinson’s disease (PD) patients and controls by microarray technology and analysis of related molecular pathways by functional annotation. Methods: Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein-protein interaction analyses were performed with STRING. Expression levels of randomly selected 5 genes among DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in peripheral blood mononuclear cells. Results: A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Discussion: Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the attempt of the immune system to suppress ongoing inflammation. Conclusion: Altered functions of Tregs might have an important role in PD pathogenesis and CD49d expression could be a prognostic biomarker of PD.

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CD49d^-Treg Cells with High Suppressive Capacity are Remarkably Less Efficient on Activated CD45RA^-than on Naive CD45RA⁺Teff Cells

Cited by 19 publications

References 31 publications

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells

Identification of Molecular Mechanisms in Parkinson’s Disease Pathogenesis: Significance of Survival and Inflammation Pathways

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