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

Front Immunol. 2023 Mar 9;14:1091541. doi: 10.3389/fimmu.2023.1091541. eCollection 2023.


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.

Keywords: imiquimod-induced psoriasis mouse model; inducible nitric oxide synthase; interleukin-35; myeloid-derived suppressor cell; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Imiquimod
  • Interleukins / genetics
  • Interleukins / metabolism
  • Mice
  • Mice, Knockout
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Psoriasis* / metabolism


  • Imiquimod
  • Nitric Oxide Synthase Type II
  • Interleukins

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province [grant numbers ZR2020KH033, ZR2021MH287, ZR2020MH163]; the National Natural Science Foundation of China [grant numbers 81801557, 81874169, 82171810, 81901587]; Research Fund for Academician Lin He New Medicine [JYHL2022ZD02, JYHL2021ZD01, JYHL2021MS06]; the Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program [grant number 2021KJ074]; the Doctoral Startup Fund of Jining Medical University [grant number JY2016QD030]; the NSFC Cultivation Project of Jining Medical University [grant number JYP2018KJ22]; and the Projects of Medical and Health Technology Development Program in Shandong Province [grant number 2019WS356].