Fig 2: Simultaneous downregulation of PTP1B and TC-PTP enhances moDCs maturation. (A) Comparisons between double heterozygous (1B:TCfl/wt) and TCfl/wt moDCs, 1Bfl/wt moDCs and wt moDCs respectively. MFI values of the expression of MHC class I, CD86 and CD80 (n = 5). (B) Production of Th1 polarizing cytokines (n = 5): (B) IL-12 and (C) IFN?. (D) Quantification of IFN? produced by activated OT-I CD8+ T cells co-cultured with mature and OVA-pulsed 1B:TCfl/wt, 1Bfl/wt, TCfl/wt or wt moDCs for 48 h (n = 8–9). (E) Quantification of IFN? produced by activated OT-II CD4+ T cells co-cultured with mature and OVA-pulsed 1B:TCfl/wt, 1Bfl/wt, TCfl/wt or wt moDCs for 48 h (n = 5). (F) Activation status of Src kinase and IkBa downstream of TLR4 (n = 3). Significant differences are represented by p values and (*) indicate significant differences between wt DCs and the rest of the groups. (G) Activation status of STAT1, STAT4 and Src in STAT1 inhibitor (fludarabine) or STAT4 inhibitor (lisofylline) treated or non-treated 1B:TCfl/wt, 1Bfl/wt, TCfl/wt or wt moDCs (n = 3). Production of Th1-polarizing cytokines by 1B:TCfl/wt, 1Bfl/wt, TCfl/wt or wt moDCs previously treated with STAT1- or STAT4-inhibitor during the maturation process (n = 3): (H) IL-12 and (I) IFN?. The results are representative of at least three independent experiments. Significant differences among the groups are represented by p values and (*) indicate significant differences within a group. The comparisons were determined using One-Way ANOVA (Holm–Sidak multiple comparison test) for parametric and Dunn's multiple test for non-parametric.

Fig 3: ITPR3 knockdown suppressed BCa cell distant metastasis in vivo. a Schematic diagram of the tail vein injection metastasis model in nude mice. b Representative bioluminescence images from the shITPR3 and shCon groups are shown in the left panel. c The histological changes detected by HE staining of the lungs from the shITPR3 and shCon groups are shown in the right panel. Arrows: foci of lung metastasis. d The general appearance of the lungs from the shITPR3 and shCon groups is presented in the left panel. e The number of lung surface metastatic lesions from the shITPR3 and shCon groups was also calculated. f The body weight changes in the shITPR3 and shCon groups were measured and recorded every three days. g Representative images of immunohistochemistry staining of ITPR3, CD44, E-cadherin, N-cadherin and IKBa are presented below. The scale bar represents 50 µm

Fig 4: (A) NFKB1 gene expression; (B) NFkBp50 Western blot analysis; (C) phosphorylated (p)-NF?Bp50 Western blot analysis; (D) NFKB2 gene expression; (E) p-NF?Bp52 Western blot analysis; (F) NFKB3 gene expression; (G) NF?Bp65 Western blot analysis; (H) p-NFkBp65 Western blot analysis; (I) NFKBIA gene expression; (J) I?Ba Western blot analysis; (K) p- I?Bß Western blot analysis; (L) NFKBIB gene expression; (M) NFKBIE gene expression; (N) IKBKG gene expression. The position (arrow) and molecular size (in kD) of the investigated proteins are indicated on each of the Western blot membrane images. Cofilin 1 was used as loading control. The vertical lines indicate group separation giving n = 5 per group.

Fig 5: Differential regulation of enhancers and promoters of IL-1a target loci NF-?B (p65), histone marks, and RNA polymerase II enrichment at the IL8 and CXCL2 promoter and enhancer in control (empty vector) or mutated (?p65eIL8 and ?p65eCXCL2) HeLa lines were assessed by ChIP-qPCR (mean enrichment over input ± SEM) at the indicated times after IL-1a stimulation. IgG, H3K27ac, H3K4me1, H3, and p65 ChIP-qPCR data are from three (vector, ?p65eCXCL2) or four (?p65EIL8) independent experiments performed in duplicate; all others are from at least two independent experiments. *: significantly different to vector controls; P < 0.01, unpaired, two-tailed Student's t-test.As in panel (A), but for the promoters of the IL6, CCL20, NFKBIA, CXCL1, and CXCL3 genes. Data are derived from at least two independent experiments (mean ± SEM, *P < 0.01, unpaired, two-tailed Student's t-test).