Chromogranin A and Its Derived Peptides in the Rat and Procine Gastro-Entero-Pancreatic System

Curry, William; Norlén, Per; Barkatullah, Sharon C.; Johnston, C.F.; Håkanson, R.; Hutton, John C.

doi:10.1007/0-306-46837-9_16

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…However, their usefulness has been somewhat limited because their antigenic target was not known. We show here that the source of the antigen for a major cohort of these clones is ChgA, a protein found in the secretory granules of pancreatic beta cells and other neuroendocrine tissues 22,23 . We also show that WE14, a natural 14 amino acid cleavage product of ChgA 13 , when presented by I-A g7 APCs, activated the ChgA-specific T cell clones in vitro .…”

Section: Discussionmentioning

confidence: 85%

Chromogranin A is an autoantigen in type 1 diabetes

et al. 2010

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Autoreactive CD4+ T cells are involved in the pathogenesis of many autoimmune diseases, but the antigens that stimulate their responses have been difficult to identify and in most cases are not well defined. In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), we have identified a peptide WE14 from chromogranin A (ChgA) as the antigen for highly diabetogenic CD4+ T cell clones. Truncation and extension analysis showed that WE14 binds to the NOD mouse MHCII molecule, I-Ag7, in an atypical manner, occupying only the C-terminal half of the I-Ag7 peptide-binding groove. This finding extends the list of T cell antigens in T1D and supports the idea that autoreactive T cells respond to unusually presented self-peptides.

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Section: Discussionmentioning

confidence: 85%

Chromogranin A is an autoantigen in type 1 diabetes

et al. 2010

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“…Gut inflammation could lead to presentation of sequestered self-antigens that are already present in the intestinal tissue. For example, chromogranin A, an islet-antigen that is capable to stimulate the diabetogenic BDC2.5 T cell clone (54), is expressed in the gastro-entero-pancreatic system (55, 56) and, under chronic inflammatory conditions, could be presented to islet-reactive T cells in the intestine. Our data do not support this idea by showing that gut inflammation by itself in DSS- BDC2.5XNOD mice depleted of endogenous microbiota is not capable to activate beta cell autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Loss of gut barrier integrity triggers activation of islet-reactive T cells and autoimmune diabetes

Sorini

Cosorich

Conte

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

161

118

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Low-grade intestinal inflammation and alterations of gut barrier integrity are found in patients affected by extraintestinal autoimmune diseases such as type 1 diabetes (T1D), but a direct causal link between enteropathy and triggering of autoimmunity is yet to be established. Here, we found that onset of autoimmunity in preclinical models of T1D is associated with alterations of the mucus layer structure and loss of gut barrier integrity. Importantly, we showed that breakage of the gut barrier integrity in BDC2.5XNOD mice carrying a transgenic T cell receptor (TCR) specific for a beta cell autoantigen leads to activation of islet-reactive T cells within the gut mucosa and onset of T1D. The intestinal activation of islet-reactive T cells requires the presence of gut microbiota and is abolished when mice are depleted of endogenous commensal microbiota by antibiotic treatment. Our results indicate that loss of gut barrier continuity can lead to activation of islet-specific T cells within the intestinal mucosa and to autoimmune diabetes and provide a strong rationale to design innovative therapeutic interventions in “at-risk” individuals aimed at restoring gut barrier integrity to prevent T1D occurrence.

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“…Although the use of cryopreserved semen for artificial insemination (AI) has spread worldwide on a commercial basis for cattle (Curry et al 2000), this has not been the case for pigs, where extended semen in liquid form still dominates and !1% of frozen semen is used mostly in genetic nuclei or for export (Eriksson & RodriguezMartinez 2000). Among the reasons for this is the better survival rate, with fertilising capacity intact, of liquid semen that, under farm or farmer AI conditions, provides almost the same prolificacy (number of piglets born) as natural mating.…”

Section: Introductionmentioning

confidence: 99%

Effects of cryopreservation on semen quality and the expression of sperm membrane hexose transporters in the spermatozoa of Iberian pigs

Sancho

Casas²,

Ekwall³

et al. 2007

Reproduction

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This study evaluated the effects of cooling, freezing and thawing on the plasma membrane integrity, kinetics and expression of two sugar transporters glucose transporter-3 and -5 (GLUT-3 and GLUT-5) in spermatozoa from Iberian boars. Semen samples were collected twice weekly from eight young, fertile Iberian boars of the 'Entrepelado' and 'Lampiñ o' breeds. The samples were suspended in a commercial extender and refrigerated to 17 8C for transport to the laboratory (step A), where they were further extended with a lactose-egg yolk-based extender and chilled to 5 8C (step B) prior to freezing in the presence of glycerol (3%). Spermatozoa were assessed for plasma membrane integrity and sperm motility at each of the steps, including post-thaw (step C). Aliquots were also prepared for immunocytochemical localisation of the sugar transporters (fixed and thin smears for transmission and scanning electron microscopy levels respectively) and for SDS-PAGE electrophoresis and subsequent western blotting, using the same antibodies (rabbit anti-GLUT-3 and anti-GLUT-5 polyclonal antibodies). The results showed lower percentages of progressively motile spermatozoa at step C in both breeds, while the percentage of live spermatozoa was significantly lower only in the 'Entrepelado' breed. The results obtained from electron microscopy clearly showed that Iberian boar spermatozoa expressed the hexose transporters, GLUT-3 and GLUT-5. The pattern of expression, in terms of location and concentration, was characteristic in each case but, in the case of isoform GLUT-5, it remained constant during the different steps of freezing-thawing protocol. These results indicate that cryopreservation affects the status of sperm cells of Iberian boars by altering the distribution of some membrane receptors and decreasing the percentage values of parameters linked to sperm quality.

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Chromogranin A and Its Derived Peptides in the Rat and Procine Gastro-Entero-Pancreatic System

Cited by 8 publications

References 25 publications

Chromogranin A is an autoantigen in type 1 diabetes

Chromogranin A is an autoantigen in type 1 diabetes

Loss of gut barrier integrity triggers activation of islet-reactive T cells and autoimmune diabetes

Effects of cryopreservation on semen quality and the expression of sperm membrane hexose transporters in the spermatozoa of Iberian pigs

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