3.8 Adoptive transfer of iNOS-/- MDSCs had no
effect on the function of IL-35 in mice with IMQ-induced psoriasis
To explore whether iNOS+ MDSCs play an important role
in the pathogenesis of psoriasis, MDSCs from WT or
iNOS-/- IMQ-induced mice were adoptively transferred
following the experimental schedule in Fig. 6A. The adoptive transfer of
WT-MDSCs derived from mice with IMQ-psoriasis mice aggravated disease
progression in the PBS group (PBS + WT-MDSCs). However, there was no
exacerbation of symptoms when MDSCs from IMQ-induced
iNOS-/- mice were transferred to the PBS group (PBS +
iNOS-/--MDSCs) (Fig. 8A). Moreover, when WT-MDSCs were
transferred to the IL-35-treated group, the psoriasis symptoms were
aggravated in these mice compared with those treated with IL-35 alone;
however, there was no significant difference in conditions between the
IL-35 + iNOS-/--MDSC and IL-35 treatment groups (Fig.
8A).
Subsequently, we evaluated the pathological features in mice, such as
erythema, scaling, and thickness in different groups using the PASI
scoring system (Fig. 8B). Compared with the PBS group, the PBS + WT-MDSC
group exhibited a higher PASI score. Similarly, the score of the IL-35 +
WT-MDSC group was significantly higher than that of the group treated
with IL-35 alone. However, the score of the PBS +
iNOS-/--MDSC group was similar to that of the PBS
group. Furthermore, there was no significant difference in scores
between IL-35 + iNOS-/- - MDSC and IL-35 treatment
groups. Finally, we calculated the cumulative scores from different
groups and found that the score of PBS + iNOS-/--MDSC
group was similar to that of the PBS group, and the IL-35-treated group
exhibited the same cumulative score as IL-35 + iNOS-/-- MDSC group (Fig. 8B). H&E-stained skin sections from these groups
showed increased epidermal thickening, serious hyperkeratosis, and
incomplete keratosis in the PBS + WT-MDSC group relative to that of the
control group. PBS + iNOS-/- - MDSC group exhibited
reduced hyperkeratosis and incomplete keratosis compared to PBS +
WT-MDSC group but almost the same morphology as that of PBS group. We
also found that the thickness of the skin epidermis in the IL-35 +
WT-MDSC group was significantly thicker than that in the IL-35-treated
group; however, IL-35 + iNOS-/--MDSC group exhibited
almost the same morphology as that of the IL-35 group (Fig. 8C). In
addition, the Baker system-based score of the IL-35-treated group was
the lowest of these six groups (Fig. 8D), and these Baker scores were
consistent with the phenotype of every group.