Effect of IL4 and IL10 on a human in vitro type 1 diabetes model

Clin Immunol. 2022 Aug:241:109076. doi: 10.1016/j.clim.2022.109076. Epub 2022 Jul 8.

Abstract

We defined the effect of the anti-inflammatory cytokines IL4 and IL10 on an in vitro model of human T1D. After preincubation with IL4 or IL10, human islet microtissues were co-cultured with PBMC and proinflammatory cytokines for a few hours or for multiple days to assess acute and chronic effects. This resulted in an immune attack with infiltration of T cells into the islet, a loss of beta cell endocrine function, and an upregulation of HLA-I on the beta cells. HLA-I upregulation was associated with infiltration of T cells and both HLA-I expression and infiltration were associated with impaired insulin secretion. Preincubation with IL4 or IL10 did not preserve beta cell function but decreased infiltration of T cells. Our data support the hypothesis that a loss of beta cell endocrine function mediates an increase in beta cell specific antigen presentation. IL4 and IL10 failed to preserve beta cell endocrine function.

Keywords: Anti-inflammatory cytokines; Human T1D model; IL10; IL4; Type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines
  • Diabetes Mellitus, Type 1*
  • Humans
  • Interleukin-10*
  • Interleukin-4 / pharmacology
  • Leukocytes, Mononuclear / metabolism

Substances

  • Cytokines
  • IL10 protein, human
  • Interleukin-10
  • Interleukin-4