Abstract
Background and Purpose :
Psoriasis is an immune-associated disease, however, the pathogenesis of
psoriasis remains unclear. We investigated the mechanism of IL-35 in
psoriasis treatment.
Experimental Approach : PASI and Baker scores were used to
evaluate the Imiquimod-induced psoriasis mouse model. Flow cytometry is
used to detect changes in immune cells and to select target cells. The
changes of inflammatory factors were detected by ELISA. Adoptive
transfused was used to demonstrate the effect of the corresponding
cells.
Key Results : IL-35 expression in patients with psoriasis was
significantly increased. The number of myeloid-derived suppressor cells
(MDSCs) in patients was also significantly increased. Similar results
were obtained in mice with imiquimod (IMQ)-induced psoriasis.
IL-35
had potent immunosuppressive effects on psoriasis model mouse, leading
to a decrease in the total number of MDSCs and its subtypes in the
spleen and psoriatic skin
lesions.
The
level of inducible nitric oxide synthase (iNOS ) secreted by MDSCs
also decreased significantly; however, there was no difference in the
level of IL-10 in MDSCs. Adoptive transfer of MDSCs from IMQ-challenged
mice weakened the effect of IL-35. When MDSCs were isolated fromiNOS knockout mice that were established with IMQ and transfected
into IMQ-induced WT mice, there was no significant difference in
psoriasis area and severity index scores between IL-35 +
iNOS-/--MDSC and IL-35 treatment groups.
Conclusions and Implications : IL-35 plays an important
immunosuppressive role in psoriasis by inhibiting the counts of
MDSCs expressing iNOS. This study may serve as a new
therapeutic
strategy for patients with chronic psoriasis or other cutaneous
inflammatory diseases.
Keywords:interleukin-35;
psoriasis; myeloid-derived suppressor cell; imiquimod-induced psoriasis
mouse model; inducible nitric oxide synthase