In Obese Patients With Type 2 Diabetes, Mast Cells in Omental Adipose Tissue Decrease the Surface Expression of CD45, CD117, CD203c, and FcϵRI

López-Pérez, David; Redruello-Romero, Anaïs; García-Rubio, Jesús; Arana, Carlos; García-Escudero, Luis Ángel; Tamayo, Francisco; Salmerón, Javier; Gálvez, Júlio; León, Josefa; Carazo, Ángel

doi:10.3389/fendo.2022.818388

Cited by 6 publications

(8 citation statements)

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“…In recent years, many studies have reported that CD45 had promoted the development of diabetes and its metabolic syndrome. Studies have confirmed that the expression of PTPRC was related to β-cell function in DM, which directly influenced insulin secretion and glycemic control ( 23 ). Our results indicated that a higher expression of PTPRC was closely related to DN.…”

Section: Discussionmentioning

confidence: 94%

Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy via Novel Biomarkers and Competing Endogenous RNA Network

et al. 2022

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Diabetic nephropathy (DN) is one of the common chronic complications of diabetes with unclear molecular mechanisms, which is associated with end-stage renal disease (ESRD) and chronic kidney disease (CKD). Our study intended to construct a competing endogenous RNA (ceRNA) network via bioinformatics analysis to determine the potential molecular mechanisms of DN pathogenesis. The microarray datasets (GSE30122 and GSE30529) were downloaded from the Gene Expression Omnibus database to find differentially expressed genes (DEGs). GSE51674 and GSE155188 datasets were used to identified the differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), respectively. The DEGs between normal and DN renal tissues were performed using the Linear Models for Microarray (limma) package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the mechanisms of DEGs in the progression of DN. The protein–protein interactions (PPI) of DEGs were carried out by STRING database. The lncRNA–miRNA–messenger RNA (mRNA) ceRNA network was constructed and visualized via Cytoscape on the basis of the interaction generated through the miRDB and TargetScan databases. A total of 94 significantly upregulated and 14 downregulated mRNAs, 31 upregulated and 121 downregulated miRNAs, and nine upregulated and 81 downregulated lncRNAs were identified. GO and KEGG pathways enriched in several functions and expression pathways, such as inflammatory response, immune response, identical protein binding, nuclear factor kappa b (NF-κB) signaling pathway, and PI3K-Akt signaling pathway. Based on the analysis of the ceRNA network, five differentially expressed lncRNAs (DElncRNAs) (SNHG6, KCNMB2-AS1, LINC00520, DANCR, and PCAT6), five DEmiRNAs (miR-130b-5p, miR-326, miR-374a-3p, miR-577, and miR-944), and five DEmRNAs (PTPRC, CD53, IRF8, IL10RA, and LAPTM5) were demonstrated to be related to the pathogenesis of DN. The hub genes were validated by using receiver operating characteristic curve (ROC) and real-time PCR (RT-PCR). Our research identified hub genes related to the potential mechanism of DN and provided new lncRNA–miRNA–mRNA ceRNA network that contributed to diagnostic and potential therapeutic targets for DN.

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Section: Discussionmentioning

confidence: 94%

Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy via Novel Biomarkers and Competing Endogenous RNA Network

et al. 2022

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“…Obesity increases the infiltration of neutrophils and reduces the number of resident mast cells ( 9 , 10 ). Furthermore, obesity induces a pro-inflammatory phenotypic switching in macrophages and disrupts the function of mast cells ( 11 , 29 ). This state of low-level chronic inflammation, together with other factors (such as adipocyte hypertrophy, fibrosis, or tissue hypoxia) impairs the normal function of adipose tissue, promoting obesity-associated pathologies.…”

Section: Discussionmentioning

confidence: 99%

Human adipose tissue as a major reservoir of cytomegalovirus-reactive T cells

Redruello-Romero,

Benitez-Cantos,

Lopez-Perez

et al. 2023

Front. Immunol.

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IntroductionCytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective.MethodsWe performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry.ResultsHigh-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells.DiscussionOverall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense.

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“…Antigenic density was performed following the protocol developed by Lopez-Perez et al. ( 34 ). Briefly, the cells were washed with PBS and incubated with 2 µL of BV421 Mouse Anti-Human Alkaline Phosphatase (BD Biosciences) for 20 minutes.…”

Section: Methodsmentioning

confidence: 99%

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene

Martínez-Heredia,

Muñoz-Torres,

Sanabria-de la Torre

et al. 2024

Front. Endocrinol.

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IntroductionHypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease.MethodsPatients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry.ResultsTwo previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction.ConclusionsThe two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.

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In Obese Patients With Type 2 Diabetes, Mast Cells in Omental Adipose Tissue Decrease the Surface Expression of CD45, CD117, CD203c, and FcϵRI

Cited by 6 publications

References 57 publications

Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy via Novel Biomarkers and Competing Endogenous RNA Network

Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy via Novel Biomarkers and Competing Endogenous RNA Network

Human adipose tissue as a major reservoir of cytomegalovirus-reactive T cells

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene

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