1. Introduction
Psoriasis
is a chronic inflammatory immune-mediated skin disease caused by
vascular hyperplasia, abnormal keratinocyte proliferation, and
inflammatory cell infiltration into the epidermis and dermis. These
extensive inflammatory cell infiltrates include T-lymphocytes, mast
cells, macrophages, myeloid-derived suppressor cells (MDSCs), and
neutrophils (Lebwohl, 2018). Studies on the pathogenesis of psoriasis
have greatly increased our understanding of skin immunology and
facilitated the introduction of innovative and efficient therapies.
However, at present, psoriasis pathogenesis is incompletely understood.
MDSCs are immature heterogeneous myeloid-derived progenitor cells and
can be divided into two cell subtypes, mononuclear MDSCs (M-MDSCs) and
polymorphonuclear MDSCs (PMN-MDSCs), also known as granulocytic MDSCs
(G-MDSCs) (Bronte et al., 2016; Tcyganov, Mastio, Chen & Gabrilovich,
2018).
MDSCs have been demonstrated to modulate immune responses in
inflammatory bowel disease (IBD) (Haile et al., 2008; Wang, Ding, Deng,
Zheng & Wang, 2020),
transplantation
(Dugast et al., 2008; Pengam et al., 2019), many types of cancer
(Diaz-Montero, Salem, Nishimura, Garrett-Mayer, Cole & Montero, 2009;
Hoechst et al., 2008; Youn, Nagaraj, Collazo & Gabrilovich, 2008), and
infections
(De Santo et al., 2008; Li et al., 2020). Recent studies have revealed
the expansion of MDSC populations, which produce cytokines including
IL-23, IL-1β, and C-C motif chemokine ligand 4 (CCL4), in patients with
psoriasis
(Cao et al., 2016; Chen et al., 2020; Oka et al., 2017; Soler &
McCormick, 2011). M-MDSCs express high levels of inducible nitric oxide
synthase (iNOS), which is a mediator of the suppressive function of
M-MDSCs in cancer (Mundy-Bosse et al., 2011). MDSCs function as immune
disruptors in patients with systemic lupus erythematosus (SLE) in an
iNOS-dependent manner. The number of M-MDSCs and the expression of iNOS
decreased after treatment, suggesting that these cells can be used as an
indicator of treatment effectiveness (Wang et al., 2019).
IL-35 is a novel inhibitory cytokine, consisting of Epstein-Barr
virus-induced gene 3 (EBI3) and IL-12 chain (p35) subunits that belong
to the IL-12 cytokine family (Collison et al., 2007). IL-35 has two
major effects including the inhibition of T-cell proliferation in
various disease models (Kochetkova, Golden, Holderness, Callis &
Pascual, 2010; Wirtz, Billmeier, McHedlidze, Blumberg & Neurath, 2011)
and inhibition of the development and differentiation of Th17 cells
(Collison et al., 2010; Collison, Pillai, Chaturvedi & Vignali, 2009).
IL-35 gene therapy significantly alleviated psoriasis-like symptoms in
psoriasis mouse models (Zhang et al., 2016). However, the contribution
of IL-35 recombinant protein to the pathogenesis of psoriasis is not
fully understood.
Therefore,
in this study, we aimed to investigate the role of the IL-35 recombinant
protein in the pathogenesis of psoriasis.