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| Item Type: | Article |
|---|---|
| Title: | A vascular-associated fibroblastic cell controls pancreatic islet immunity |
| Creators Name: | Clarke, Don, Costanzo, Anne, Sharma, Siddhartha, Kain, Lisa, Moremen, Kelley W., Pettus, Jeremy, Domissy, Alain, Wu, Peng, Nguyen-Ngoc, Kim-Vy, Berti, Denise, George, Steven C., Hughes, Christopher C.W., Sander, Maike and Teyton, Luc |
| Abstract: | The immune protection of pancreatic β cells has three layers: anatomical, with their distribution in 1 million islets; central, with the thymic deletion of β cell-specific T cells; and peripheral, with inhibitory cellular networks. The failure of the latter leads to most spontaneous type 1 diabetes and all diabetes induced by checkpoint inhibitor therapy. Because CD4 T cells initiate disease, major histocompatibility complex (MHC) class II-expressing cells are central to the onset. In non-diabetic mouse and human islets, two such cells were detected outside of the islet boundaries near the efferent post-capillary venules: one related to the vasculature and a fibroblast referred to as a "vascular-associated fibroblast" (VAF). Functionally, primary VAFs spontaneously presented islet antigens to CD4 T cells and expressed high levels of inhibitory B7 receptors and no costimulatory receptors. VAFs induced anergy in primary pre-activated anti-islet CD4 T cells. VAFs are likely important to protect the endocrine pancreas from autoimmunity. |
| Keywords: | CD4-Positive T-Lymphocytes, Fibroblasts, Inbred C57BL Mice, Islets of Langerhans, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 44 |
| Number: | 9 |
| Page Range: | 116189 |
| Date: | 23 September 2025 |
| Additional Information: | Accession "GSE292898" is currently private and is scheduled to be released on Mar 15, 2029. |
| Official Publication: | https://doi.org/10.1016/j.celrep.2025.116189 |
| PubMed: | View item in PubMed |
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