ISSN 1662-4009 (online)

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Yearbook of Paediatric Endocrinology 2023

8. Type 1 Diabetes

New Mechanisms

ey0020.8-11 | New Mechanisms | ESPEYB20

8.11. Soluble RAGE prevents type 1 diabetes expanding functional regulatory T cells

SS Leung , DJ Borg , DA McCarthy , TE Boursalian , J Cracraft , A Zhuang , AK Fotheringham , N Flemming , T Watkins , JJ Miles , PH Groop , JL Scheijen , CG Schalkwijk , RJ Steptoe , KJ Radford , M Knip , JM Forbes

Brief summary: using a murine model of diabetes and ex vivo experiments in human T-cell cultures, this study showed that short-term administration of an antagonist to the receptor for advanced glycation end products (sRAGE) modulates functional T regulatory cells (Treg) expansion and thus prevents diabetes.This study provides further support for a role of the advanced glycation end-product (AGEs)-AGE receptor (RAGE) pathways in the pathogenesis ...

ey0020.8-12 | New Mechanisms | ESPEYB20

8.12. ZnT8 loss-of-function accelerates functional maturation of hESC-derived beta cells and resists metabolic stress in diabetes

Q Ma , Y Xiao , W Xu , M Wang , S Li , Z Yang , M Xu , T Zhang , ZN Zhang , R Hu , Q Su , F Yuan , T Xiao , X Wang , Q He , J Zhao , ZJ Chen , Z Sheng , M Chai , H Wang , W Shi , Q Deng , X Cheng , W Li

Brief summary: In this experimental study, genome editing and in vitro pancreatic differentiation of human pluripotent stem cells (SC) were used to generate ZNT8 loss-of-function (LOF) SC-β-cells. These cells showed accelerated functional maturation, increased insulin secretion and improved resistance to metabolic stress. Transplantation of ZnT8 LOF SC-β-cells into mice with preexisting diabetes significantly improved their glucose levels.<...

ey0020.8-13 | New Mechanisms | ESPEYB20

8.13. Low-dose IL-2 reduces IL-21(+) T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

JY Zhang , F Hamey , D Trzupek , M Mickunas , M Lee , L Godfrey , JHM Yang , ML Pekalski , J Kennet , F Waldron-Lynch , ML Evans , TIM Tree , LS Wicker , JA Todd , RC Ferreira

Brief summary: This study used high-resolution single-cell multiomics and flow cytometry on blood samples from patients with type 1 diabetes (T1D) to examine the effects of low-dose recombinant IL-2 (iLD-IL-2). Administration of iLD-IL-2 expanded thymic-derived FOXP3+HELIOS+ Tregs and CD56bright NK cells, reduced frequency of IL-21-producing CD4+T cells, and induced long-lived anti-inflammatory transcriptional changes in all T and NK...