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Islet transplantation into brown adipose tissue can delay immune rejection

Abstract:
Type 1 diabetes is an autoimmune disease characterized by insulin-producing β cell destruction. Although islet transplantation restores euglycemia and improves patient outcomes, an ideal transplant site remains elusive. Brown adipose tissue (BAT) has a highly vascularized and antiinflammatory microenvironment. Because these tissue features can promote islet graft survival, we hypothesized that islets transplanted into BAT will maintain islet graft and BAT function while delaying immune-mediated rejection. We transplanted syngeneic and allogeneic islets into BAT or under the kidney capsule of streptozotocin-induced diabetic NOD.Rag and NOD mice to investigate islet graft function, BAT function, metabolism, and immune-mediated rejection. Islet grafts within BAT restored euglycemia similarly to kidney capsule controls. Islets transplanted in BAT maintained expression of islet hormones and transcription factors and were vascularized. Compared with those in kidney capsule and euglycemic mock-surgery controls, no differences in glucose or insulin tolerance, thermogenic regulation, or energy expenditure were observed with islet grafts in BAT. Immune profiling of BAT revealed enriched antiinflammatory macrophages and T cells. Compared with the kidney capsule control, there were significant delays in autoimmune and allograft rejection of islets transplanted in BAT, possibly due to increased antiinflammatory immune populations. Our data support BAT as an alternative islet transplant site that may improve graft survival.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1172/jci.insight.152800

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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0002-0600-2045
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Role:
Author
ORCID:
0000-0002-6456-9293
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Role:
Author
ORCID:
0000-0001-8360-5029
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Role:
Author
ORCID:
0000-0002-1644-447X
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Role:
Author
ORCID:
0000-0001-5861-7597


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Funder identifier:
10.13039/100000002
Grant:
DK099550
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Grant:
SRA-2016-270-S-B


Publisher:
American Society for Clinical Investigation
Journal:
JCI Insight More from this journal
Volume:
7
Issue:
4
Pages:
e152800
Article number:
e152800
Publication date:
2022-02-22
DOI:
EISSN:
2379-3708
ISSN:
2379-3708


Language:
English
Keywords:
Pubs id:
1236006
Local pid:
pubs:1236006
Source identifiers:
W4206409604
Deposit date:
2026-04-09
ARK identifier:
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