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.