Inducible nitric oxide synthase-expressing myeloid-derived suppressor cells regulated by interleukin 35 contribute to the pathogenesis of psoriasis

Junfeng Zhang, Yunsheng Zhang, Zhiya Yang, Dalei Cheng, Hui Zhang, Li Wei, Chen Liu, Fenglian Yan, Chunxia Li, Guanjun Dong, Changying Wang, Dongmei Shi, Huabao Xiong

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Although psoriasis is classified as a T cell-mediated inflammatory disease, the contribution of myeloid cells to the pathogenesis of psoriasis is not fully understood. In the present study, we demonstrated that the expression of the anti-inflammatory cytokine interleukin-35 (IL-35) was significantly increased in patients with psoriasis with a marked increase in the number of myeloid-derived suppressor cells (MDSCs). Similar results were obtained in an imiquimod-induced psoriasis mouse model. IL-35 reduced the total number of MDSCs and their subtypes in the spleens and psoriatic skin lesions, ameliorating psoriasis. IL-35 also reduced the expression of inducible nitric oxide synthase in MDSCs, although it had no significant effect on interleukin-10 expression. Adoptive transfer of MDSCs from imiquimod-challenged mice aggravated the disease and weakened the effect of IL-35 in the recipient mice. In addition, mice transferred with MDSCs isolated from inducible nitric oxide synthase knockout mice had milder disease than those with wild-type MDSCs. Furthermore, wild-type MDSCs reversed the effects of IL-35, while MDSCs isolated from inducible nitric oxide synthase knockout mice did not affect IL-35 treatment. In summary, IL-35 may play a critical role in the regulation of iNOS-expressing MDSCs in the pathogenesis of psoriasis, highlighting IL-35 as a novel therapeutic strategy for patients with chronic psoriasis or other cutaneous inflammatory diseases.

Original languageEnglish
Article number1091541
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • imiquimod-induced psoriasis mouse model
  • inducible nitric oxide synthase
  • interleukin-35
  • myeloid-derived suppressor cell
  • psoriasis

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