Detection of vasostatin-1-specific CD8+ T cells in non-obese diabetic mice that contribute to diabetes pathogenesis

Nikoopour, Enayat; Krougly, Olga; Lee-Chan, Edwin; Haeryfar, S.M. Mansour; Singh, Bhagirath

doi:10.1111/cei.12811

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…HLA-A3 1 patients with new-onset T1D (n 5 9; median age 26 years [range [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]; median disease duration 1.4 weeks [range 0.3-32]) and age/sex-matched healthy donors (Supplementary Table 1) gave written informed consent under ethics approval DC-2015-2536 Ile-de-France I. HLA-A3 (A*03:01) typing was performed with AmbiSolv primers (Dynal/Thermo Fisher Scientific). Blood was drawn into 9-mL sodium heparin tubes and peripheral blood mononuclear cells (PBMCs) isolated and frozen as described (3,28).…”

Section: Study Participants and Blood Processingmentioning

confidence: 99%

Peptides Derived From Insulin Granule Proteins Are Targeted by CD8+ T Cells Across MHC Class I Restrictions in Humans and NOD Mice

et al. 2020

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The antigenic peptides processed by β-cells and presented through surface HLA class I molecules are poorly characterized. Each HLA variant (e.g., the most common being HLA-A2 and HLA-A3) carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of the HLA-A2/A3 peptidome of β-cells, we analyzed the HLA-A3–restricted peptides targeted by circulating CD8+ T cells. Several peptides were recognized by CD8+ T cells within a narrow frequency (1–50/106), which was similar in donors with and without type 1 diabetes and harbored variable effector/memory fractions. These epitopes could be classified as conventional peptides or neoepitopes, generated either via peptide cis-splicing or mRNA splicing (e.g., secretogranin-5 [SCG5]–009). As reported for HLA-A2–restricted peptides, several epitopes originated from β-cell granule proteins (e.g., SCG3, SCG5, and urocortin-3). Similarly, H-2Kd–restricted CD8+ T cells recognizing the murine orthologs of SCG5, urocortin-3, and proconvertase-2 infiltrated the islets of NOD mice and transferred diabetes into NOD/scid recipients. The finding of granule proteins targeted in both humans and NOD mice supports their disease relevance and identifies the insulin granule as a rich source of epitopes, possibly reflecting its impaired processing in type 1 diabetes.

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Section: Study Participants and Blood Processingmentioning

confidence: 99%

Peptides Derived From Insulin Granule Proteins Are Targeted by CD8+ T Cells Across MHC Class I Restrictions in Humans and NOD Mice

et al. 2020

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“…The protein encoded by Chga , chromogranin A, is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins and a precursor to three biologically-active peptides, vasostatin, pancreastatin and parastatin. The first inhibits angiogenesis and suppresses tumor growth, the second strongly inhibits glucose-induced insulin release from the pancreas, and the third inhibits parathyroid cell secretion [38–40]. The extent of down-regulation of the other genes shown on Table 2 were greater than 2 −4.37 -fold change.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic analysis and plasma metabolomics in Aldh16a1 -null mice reveals a potential role of ALDH16A1 in renal function

Charkoftaki

Chen

Han

et al. 2017

Chemico-Biological Interactions

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ALDH16A1 is a novel member of the ALDH superfamily that is enzymatically-inactive and highly expressed in the kidney. Recent studies identified an association between a rare missense single nucleotide variant (SNV) in the ALDH16A1 gene and elevated serum uric acid levels and gout. The present study explores the mechanisms by which ALDH16A1 influences uric acid homeostasis in the kidney. We generated and validated a mouse line with global disruption of the Aldh16a1 gene through gene targeting and performed RNA-seq analyses in the kidney of wild-type (WT) and Aldh16a1 knockout (KO) mice, along with plasma metabolomics. We found that ALDH16A1 is expressed in proximal and distal convoluted tubule cells in the cortex of the kidney and in zone 3 hepatocytes. RNA-seq and gene ontology enrichment analyses showed that cellular lipid and lipid metabolic processes are up-regulated. Three transporters localized in the apical membrane of the proximal convoluted tubule of the kidney known to influence urate/uric acid homeostasis were found to be up-regulated (Abcc4, Slc16a9) or down-regulated (Slc17a3). An initial metabolomics analysis in plasma revealed an altered lipid profile in KO mice that is in agreement with our RNA-seq analysis. This is the first study demonstrating a functional role of ALDH16A1 in the kidney.

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“…CgA helps regulate secretion in granules and produces several degradation products after secretion. Some of the products obtained after CgA degradation alter hormonal functions in autocrine and paracrine ways [9,18].Recent studies [13,15,16,17,19,20,23] have shown that CgA and some of its breakdown products, namely (pancreastatin, catestatin, vasostatin 1, WE-14) play an important role in the pathogenesis of various forms of diabetes [4,6,14,18,24], but the exact mechanisms of their action are still unclear. Several studies [12,17,20] have reported higher levels of pancreastatin and WE-14 in patients with type 1 and type 2 diabetes [12].According to a number of authors [1,11,13,15,18], pancreastatin, catestatin, and vasostatin play an important role in metabolic syndromes, namely obesity, diabetes, and others.…”

mentioning

confidence: 99%

“…Recent studies [13,15,16,17,19,20,23] have shown that CgA and some of its breakdown products, namely (pancreastatin, catestatin, vasostatin 1, WE-14) play an important role in the pathogenesis of various forms of diabetes [4,6,14,18,24], but the exact mechanisms of their action are still unclear. Several studies [12,17,20] have reported higher levels of pancreastatin and WE-14 in patients with type 1 and type 2 diabetes [12].…”

mentioning

confidence: 99%

Expression of Chromogranin (Cga) in Rat Pancreas During Alloxan Diabetes

MACHAVARIANI,

LATSABIDZE,

DGEBUADZE

et al. 2024

jecm

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Introduction. Chromogranin A (CgA) lipoprotein is one of the important representatives of the group of granins. CgA is found in neuroendocrine, endocrine, and nerve cells [2,21]. CgA is a granulogenic factor that regulates secretory functions in tissues. CgA participates in the generation of secretory granules, and its breakdown products are biologically active peptides [4,8,21]. CgA helps regulate secretion in granules and produces several degradation products after secretion. Some of the products obtained after CgA degradation alter hormonal functions in autocrine and paracrine ways [9,18].Recent studies [13,15,16,17,19,20,23] have shown that CgA and some of its breakdown products, namely (pancreastatin, catestatin, vasostatin 1, WE-14) play an important role in the pathogenesis of various forms of diabetes [4,6,14,18,24], but the exact mechanisms of their action are still unclear. Several studies [12,17,20] have reported higher levels of pancreastatin and WE-14 in patients with type 1 and type 2 diabetes [12].According to a number of authors [1,11,13,15,18], pancreastatin, catestatin, and vasostatin play an important role in metabolic syndromes, namely obesity, diabetes, and others. Pancreastatin affects insulin [4,17,23], weakening insulin sensitivity and enhances inflammatory processes, while pancreastatin inhibitory peptide (PSTi8) improves insulin sensitivity and regulates glucose homeostasis [6,17,24]. In contrast, catestatin CST increases insulin sensitivity and reduces inflammatory reactions. According to a number of studies [12,17,20,23,24] pancreastatin and catestatin regulate pancreatic β-cell insulin secretion and glucose metabolism. The metabolic effect of the peptide fragments obtained after CgA cleavage allows us to speculate on their possible participation in the pathophysiology of diabetes and to use it as a

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Detection of vasostatin-1-specific CD8+ T cells in non-obese diabetic mice that contribute to diabetes pathogenesis

Abstract: SummaryChromogranin A (ChgA) is an antigenic target of pathogenic CD41 T cells in a non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D

Cited by 8 publications

References 35 publications

Peptides Derived From Insulin Granule Proteins Are Targeted by CD8+ T Cells Across MHC Class I Restrictions in Humans and NOD Mice

Peptides Derived From Insulin Granule Proteins Are Targeted by CD8+ T Cells Across MHC Class I Restrictions in Humans and NOD Mice

Transcriptomic analysis and plasma metabolomics in Aldh16a1 -null mice reveals a potential role of ALDH16A1 in renal function

Expression of Chromogranin (Cga) in Rat Pancreas During Alloxan Diabetes

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