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Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms
Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9–23 epitope points to a dominant role of insulin in diabetogenesis....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660984/ https://www.ncbi.nlm.nih.gov/pubmed/34497137 http://dx.doi.org/10.2337/db21-0513 |
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author | Srivastava, Neetu Hu, Hao Vomund, Anthony N. Peterson, Orion J. Baker, Rocky L. Haskins, Kathryn Teyton, Luc Wan, Xiaoxiao Unanue, Emil R. |
author_facet | Srivastava, Neetu Hu, Hao Vomund, Anthony N. Peterson, Orion J. Baker, Rocky L. Haskins, Kathryn Teyton, Luc Wan, Xiaoxiao Unanue, Emil R. |
author_sort | Srivastava, Neetu |
collection | PubMed |
description | Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9–23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the chromogranin A protein (NOD.ChgA(−/−)) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA(−/−) mice and found that their lack of diabetes development may not be solely explained by the absence of chromogranin A reactivity. NOD.ChgA(−/−) mice displayed reduced presentation of insulin peptides in the islets and periphery, which corresponded to impaired T-cell priming. Diabetes development in these mice was restored by antibody treatment targeting regulatory T cells or inhibiting transforming growth factor-β and programmed death-1 pathways. Therefore, the global deficiency of chromogranin A impairs recognition of the major diabetogenic antigen insulin, leading to broadly impaired autoimmune responses controlled by multiple regulatory mechanisms. |
format | Online Article Text |
id | pubmed-8660984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-86609842021-12-27 Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms Srivastava, Neetu Hu, Hao Vomund, Anthony N. Peterson, Orion J. Baker, Rocky L. Haskins, Kathryn Teyton, Luc Wan, Xiaoxiao Unanue, Emil R. Diabetes Immunology and Transplantation Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9–23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the chromogranin A protein (NOD.ChgA(−/−)) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA(−/−) mice and found that their lack of diabetes development may not be solely explained by the absence of chromogranin A reactivity. NOD.ChgA(−/−) mice displayed reduced presentation of insulin peptides in the islets and periphery, which corresponded to impaired T-cell priming. Diabetes development in these mice was restored by antibody treatment targeting regulatory T cells or inhibiting transforming growth factor-β and programmed death-1 pathways. Therefore, the global deficiency of chromogranin A impairs recognition of the major diabetogenic antigen insulin, leading to broadly impaired autoimmune responses controlled by multiple regulatory mechanisms. American Diabetes Association 2021-12 2021-09-08 /pmc/articles/PMC8660984/ /pubmed/34497137 http://dx.doi.org/10.2337/db21-0513 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. |
spellingShingle | Immunology and Transplantation Srivastava, Neetu Hu, Hao Vomund, Anthony N. Peterson, Orion J. Baker, Rocky L. Haskins, Kathryn Teyton, Luc Wan, Xiaoxiao Unanue, Emil R. Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title | Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title_full | Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title_fullStr | Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title_full_unstemmed | Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title_short | Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms |
title_sort | chromogranin a deficiency confers protection from autoimmune diabetes via multiple mechanisms |
topic | Immunology and Transplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660984/ https://www.ncbi.nlm.nih.gov/pubmed/34497137 http://dx.doi.org/10.2337/db21-0513 |
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