Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes
Aims/hypothesis B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet $ CD19^{+} %$ CD138^{–} $ and $ CD19^{+} %$ CD138^{+} $ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with $ CD138^{–} $ B cells, $ CD138^{+} $ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in $ CD138^{+} $ B cells. Conclusions/interpretation Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes. Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Diabetologia - 66(2022), 3 vom: 12. Dez., Seite 551-566 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boldison, Joanne [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| Anmerkungen: |
© The Author(s) 2022 |
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| doi: |
10.1007/s00125-022-05839-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes |
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| 520 | |a Aims/hypothesis B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet $ CD19^{+} %$ CD138^{–} $ and $ CD19^{+} %$ CD138^{+} $ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with $ CD138^{–} $ B cells, $ CD138^{+} $ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in $ CD138^{+} $ B cells. Conclusions/interpretation Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes. Graphical abstract | ||
| 650 | 4 | |a Autoimmunity |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a B cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Pancreatic islets |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a TLR7 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Type 1 diabetes |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Hopkinson, Jessica R. |4 aut | |
| 700 | 1 | |a Davies, Joanne |4 aut | |
| 700 | 1 | |a Pearson, James A. |4 aut | |
| 700 | 1 | |a Leete, Pia |4 aut | |
| 700 | 1 | |a Richardson, Sarah |4 aut | |
| 700 | 1 | |a Morgan, Noel G. |4 aut | |
| 700 | 1 | |a Wong, F. Susan |4 aut | |
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