Fig 2: IL-10 controls the IL-17A axis in the proinflammatory milieu of the postischemic brain. Relative gene expression of Il23a and Il1b in brain resident CD45intermed/CD11b+ microglia (A) and central nervous system-infiltrating CD45high/CD11b+/CD11c−/MHCII−/Ly6g−/F4/80+ macrophages (B) purified 3, 7 and 14 days after tMCAO by fluorescence activated cell sorting from ischemic hemispheres. Expression levels were normalized to corresponding levels of splenic macrophages and microglia after sham operation. C Flow cytometric analysis of IL-17A produced by CD4+ and γδ T cells isolated from ischemic hemispheres of WT controls and Il10−/− mice 7 days after tMCAO. D Flow cytometric analysis of number of infiltrating neutrophils in the ischemic hemispheres of WT controls and Il10−/− mice 3 days after tMCAO. E Frequency of IL-17A producing γδ T cells purified from ischemic brains was analyzed 3 days following tMCAO in control mice (BSA) and mice receiving IL-10 intracerebral 3 h after tMCAO induction. A, B RT-qPCR gene expression data is represented as mean ± SEM of 4–7 WT, Flow cytometric data as mean ± SEM of 6 WT and 5 Il10−/− (C), 9 WT and 7 Il10−/− mice (D), and of 7 WT mice in each treatment group (E). Statistical significances were analyzed by one-way ANOVA with Bonferroni post hoc test (A, B) and by Student t test (C–E). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001

Fig 3: Combination treatment with transcutaneous arginase inhibition and systemic PD-1 inhibition is associated with increased recruitment of intratumoral T cells and dendritic cells than either treatment, alone. (A) Percentage of intratumoral CD45+ leukocytes that are CD3+ CD4+, indicating tumor-infiltrating CD4+ T cells; combination nor-NOHA + nivolumab treatments had significantly higher proportions than either treatment alone. (B) Percentage of intratumoral CD45+ leukocytes that are CD3+ CD8+, indicating tumor-infiltrating CD8+ T cells; combination nor-NOHA + nivolumab treatments had significantly higher proportions than either treatment alone. (C) Percentage of intratumoral CD45 + leukocytes that are CD11c+ MHCII+, indicating tumor-infiltrating dendritic cells; combination nor-NOHA + nivolumab treatments had significantly higher proportions than either treatment alone. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 using the unpaired t-test adjusted for multiple comparisons. Two separate experiments with n > 5 per group.

Fig 4: Schematic diagram of how the antiviral signaling mediates psoriasis pathogenesisIn genetically predisposed individuals, the virus infection causes the activation of TLR-7/8 and/or RIG-I, and subsequently triggers IL-23 release by CD11c+ DCs via the NF-?B pathway. Genetic mutations in NF-?B-related genes result in an impaired negative regulation of its proinflammatory activity accompanied by uncontrolled IL-23 release, thus leading to psoriasis.

Fig 5: RIG‐I expression in DCs is critical for IL‐23 production Representative flow cytometry analysis of the frequency of CD45+RIG‐I+ cells in WT ears treated with PBS or IL‐23 (n = 5).Statistical analysis of the results in (A). Significant differences are indicated: two‐tailed Student's t‐test, n = 5 per group (mean ± SEM).Representative flow cytometry analysis of the frequency of RIG‐I+CD3+, RIG‐I+CD11c+, and RIG‐I+F4/80+ cells in ears treated with IL‐23 (n = 4–5).Statistical analysis of the results in (C). Significant differences are indicated: two‐tailed Student's t‐test, n = 4–5 per group (mean ± SEM).qPCR analysis of IL‐23p19 mRNA expression of cultured WT BMDCs and RIG‐I−/− BMDCs treated with indicated stimulation for 24 h. qPCR values expressed as the ratio of mRNA to β‐actin, relative to negative control, and indicated as fold change. Significant differences are indicated: two‐tailed Student's t‐test, n = 5–6 per group (mean ± SEM).ELISA detection of IL‐23p19 protein levels in supernatants of cultured WT BMDCs and RIG‐I−/− BMDCs treated with indicated stimulation for 48 h. Significant differences are indicated: two‐tailed Student's t‐test, n = 3 per group (mean ± SEM).