Pglyrp3/4 Promote Treg and Inhibit Th17 Responses Figure 7. Th17 gene expression profile is preferentially induced in the atopic dermatitis model in Pglyrp32/2 and Pglyrp42/2 mice, whereas expression of most immune genes is reduced in the contact dermatitis model in Pglyrp2/2 mice. Expression of a panel of cytokines, chemokines, and other marker genes characteristic of Th1, Th2, Th17, Treg, NK, and other cell types in the ears of mice was measured by qRT-PCR. (A) After sensitization and 10 applications of oxazolone to the ears every other day the expression of several Th17 marker genes was higher in Pglyrp32/2 and Pglyrp42/2 mice than in WT mice. (B) After sensitization and a single application of oxazolone to the ears the expression of most of immune marker genes was lower in Pglyrp2/2 mice than in WT mice. For WT mice (left panels in A and B), the ratio of the amount of mRNA in oxazolone-treated to untreated mice for each gene (fold induction by oxazolone) is shown; for Pglyrp2/2 mice (right panels in A and B), the results are the ratios of fold induction of each gene by oxazolone in Pglyrp2/2 mice to fold induction of each gene by oxazolone in WT mice (which represents the fold difference in the response to oxazolone in Pglyrp2/2 versus WT mice). The results are means of 3 arrays from 4–5 mice/group in heat map format. The means 6 SEM bar graphs for these results are shown in Figures S3, S4, and S5. doi:10.1371/journal.pone.0024961.g007 for full manifestation of severe skin inflammation in Pglyrp32/2 mice in the atopic dermatitis model. Pglyrp32/2 and Pglyrp42/2 mice have decreased numbers of Treg cells in the skin Because WT mice were able to limit skin inflammation in the atopic dermatitis model more effectively than Pglyrp32/2 and Pglyrp42/2 mice, we then tested whether this difference is due to impaired generation or function of regulatory T cells (CD4+FoxP3+ Treg) in Pglyrp-deficient mice. In the atopic dermatitis model WT mice efficiently recruited Treg cells into the affected skin, as evidenced by an increase in FoxP3-expressing Treg cells in the affected skin shown both by the qRT-PCR (Figure 6A and Figure S1) and by flow cytometry, in which high numbers of CD4+FoxP3+ Treg cells were found in the affected skin in WT mice (Figure 8B–D). By contrast, atopic dermatitis-sensitive Pglyrp-deficient mice (Pglyrp32/2, Pglyrp42/2 and Pglyrp22/2Pglyrp32/2 mice) all had lower expression of FoxP3 mRNA in the affected ears compared to WT mice (Figure 6A and Figure S1). Pglyrp32/2 mice in the atopic dermatitis model also PLoS ONE | www.plosone.org 9 September 2011 | Volume 6 | Issue 9 | e24961