Islet transplantation into brown adipose tissue can delay immune rejection.
Kepple JD., Barra JM., Young ME., Hunter CS., Tse HM.
Type 1 diabetes is an autoimmune disease characterized by insulin-producing beta-cell destruction. While islet transplantation restores euglycemia and improves patient outcomes, an ideal transplant site remains elusive. Brown adipose tissue (BAT) is a highly vascularized and anti-inflammatory microenvironment. As these tissue features can promote islet graft survival, we hypothesize that islets transplanted into BAT will maintain islet graft and BAT function, while delaying immune-mediated rejection. We performed syngeneic and allogeneic islet transplants into BAT or under the kidney capsule of streptozotocin (STZ)-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, transcription factors, and were vascularized. Compared to 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 anti-inflammatory macrophages and T cells. Compared to kidney capsule, islets transplanted in BAT demonstrated significant delays in autoimmune and allograft rejection, possibly due to increased anti-inflammatory immune populations. Our data support BAT as an alternative islet transplantation site that may improve graft survival.