Interleukin 35 regulates interleukin 17 expression and T helper 17 in patients with proliferative diabetic retinopathy

Bioengineered. 2022 May;13(5):13293-13299. doi: 10.1080/21655979.2022.2080367.

Abstract

T helper 17 (Th17) cells regulate inflammatory processes and are implicated in pathogenesis of proliferative diabetic retinopathy (PDR) through modulation of interleukin-17 (IL-17). IL-35, anti-inflammatory factor, negatively mediates IL-17 expression and Th17 differentiation. In this study, the role of IL-35 in PDR was assessed. The results showed that IL-35 was down-regulated, while IL-17 was up-regulated, in peripheral blood mononuclear cells (PBMCs) of PDR patients. In addition, immunofluorescence analysis indicated that frequency of Th17 cells was enhanced in the PBMCs of PDR patients. However, incubation with IL-35 reduced the Th17 cell frequency and decreased the level of IL-17 in CD4+ T lymphocytes. Moreover, the levels of transcription factors essential for Th17 differentiation, ROR α (retinoid-related orphan receptor alpha) and ROR γt, were reduced by IL-35 treatment. In conclusion, IL-35 reduced level of IL-17 and inhibited Th17 differentiation to protect against PDR.

Keywords: IL-17; IL-35; ROR α; ROR γt; Th17 cell; proliferative diabetic retinopathy.

MeSH terms

  • Cell Differentiation
  • Diabetes Mellitus*
  • Diabetic Retinopathy* / genetics
  • Diabetic Retinopathy* / metabolism
  • Diabetic Retinopathy* / pathology
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Leukocytes, Mononuclear
  • Th17 Cells / metabolism

Substances

  • Interleukin-17

Grants and funding

This work was supported by Zunyi Science and Technology Bureau Joint Research and Development Fund Project (Grant No. (2017)35), National Nature Science Foundation of China (Grant No. 82160200), R&D Program of The First People’s Hospital of Zunyi (Grant No. (2020)4), Science and Technology Fund Project of Guizhou Provincial Health Commission in 2020 (Grant No. gzwjk2020-1-155).