Title: Proinflammatory cytokines contribute to development and function of regulatory T cells in type 1 diabetes
Authors: Thomas, HE
Graham, KL
Chee, J
Thomas, R
Kay, TW
Krishnamurthy, B
Issue Year: 2013
Publisher BLACKWELL SCIENCE PUBL
Series TRANSLATIONAL IMMUNOLOGY IN ASIA-OCEANIA: 1283(): 81-86
Abstract Type 1 diabetes is caused by immune-mediated loss of pancreatic beta cells. It has been proposed that inflammatory cytokines play a role in killing beta cells. Expression of interleukin (IL)-1 and tumor necrosis factor (TNF-alpha) has been detected in islets from patients with type 1 diabetes, and these cytokines can induce beta cell death in vitro. We produced nonobese diabetic (NOD) mice lacking receptors for these cytokines. Islets from mice lacking IL-1RI or TNFR1 were killed when transplanted into wild-type NOD mice, suggesting that cytokine action on beta cells is not required for killing. Mice lacking TNFR1 did not develop diabetes, and mice lacking IL-1R had delayed onset of diabetes, indicating a role for these cytokines in disease development. TNFR1-deficient mice had an increased number of CD4(+)CD25(+)FoxP3(+) regulatory T cells with enhanced suppressive capacity. IL-1 was produced at higher levels in NOD mice and resulted in dilution of suppressor function of CD4(+)CD25(+)FoxP3(+) regulatory T cells. Our data suggest that blocking inflammatory cytokines may increase the capacity of the immune system to suppress type 1 diabetes through regulatory T cells.
URI: https://publications.svi.edu.au/publications/1737
ISSN 0077-8923
Other Identifiers 10.1111/j.1749-6632.2012.06797.x
Publication type Article; Proceedings Paper