Fig 1: Src homology‐2 domain‐containing protein tyrosine phosphatase (SHP2) deficiency in neutrophils alleviates psoriasis‐like phenotype in the imiquimod (IMQ)‐induced murine model. (A) Phenotypic presentation of back skin sections of sham‐ or IMQ‐treated SHP2N KO and WT mice, scale bar = 5 mm. (B) H&E staining of back skin sections of sham‐ or IMQ‐treated SHP2N KO and WT mice, scale bar = 200 μm. Clinical scores (C) and epidermal thickness (D) of mice dorsal skin. (E) Dorsal skin was infiltrated with TNF‐α, IL‐1β, IL‐6, IL‐17a, and CXCL‐15 evaluated by ELISA
Fig 2: Neutrophil extracellular traps (NETs) can mediate the pathogenesis of psoriasis associated with SHP2. Representative immunohistochemical staining of skin sections from psoriasis patients and healthy donors with anti‐PAD4 (A) or anti‐CitH3 (B), scale bar = 400 μm. (C) Representative immunofluorescence staining of skin sections from healthy donors (n = 8) and psoriasis patients (n = 13) with anti‐MPO, anti‐neutrophil elastase (NE), and 4′,6‐diamidino‐2‐phenylindole (DAPI), scale bar = 400 μm. (D) Quantification of dsDNA in serum samples from healthy and psoriasis donors. (E) The expression level of PTPN11, ELANE, and PADI4 in human skin
Fig 3: SHP-2 mediates the growth enhancing activity of and interacts with SLAMF8 in ALK-positive ALCL cells. (A) The effects of SLAMF8 knockdown on SHP-2 activation in human ALCL cell lines. SHP-2 ELISA (n = 3). *P < 0.05, compared to control cells. (B) The effects of the SHP-2 inhibitor PHPS1 on the cell growth of human ALCL cell lines. CCK-8 assay (n = 3). *P < 0.05, compared to control cells. (C) Interaction between SLAMF8 and SHP-2 or ALK in human cell lines. The DuoLink in situ kit. Red dots indicate the interaction between SLAMF8 and SHP-2 or ALK. Bars; 10 μM. (D) Interaction between SLAMF8 and SHP-2 in ALK-positive ALCL cell lines treated with crizotinib or PHPS1. Red dots indicate the interaction between SLAMF8 and SHP-2. Bars; 10 μM.
Fig 4: Single‐cell RNA sequencing reveals that SHP2 expression is related to developing psoriasis. (A) Unbiased clustering of human skin data shown by UMAP plot. (B) UMAP visualization of the distribution of cells splitting by samples. (C) Heatmap demonstrated the top five differentially expressed genes for each cluster. (D) Gene set enrichment analysis (GSEA) of different clusters and shown by UMAP plot. (E) GO pathways analysis through top genes from human skin tissue. (F) The hematoxylin and eosin (H&E) staining of the skin sections and spatial feature plot of PI3 and S100A8’s expression. (G) Representative immunohistochemical image staining for myeloperoxidase (MPO) of healthy (n = 8) and psoriasis patients (n = 13) donors, scale bar = 400 μm. (H) The violin plot of the top nine expression abundance of 107 protein tyrosine phosphatases (PTPs). (I) The spatial feature plot of S100A8 and PTPN11’s expression
Fig 5: Inhibition of SHP2 expression in neutrophils can inhibit the formation of neutrophil extracellular traps (NETs). (A) The protein expression of NE and MPO in the IMQ and/or SHP099 treated mice. (B) The protein level of CitH3 and PAD4 of mice dorsal skin, tested by western blot. (C) The protein expression of NE and MPO of mice dorsal skin tested by ELISA. (D) Representative immunofluorescence images staining for MPO (green), NE (red), and DAPI (blue) of mice skin section, scale bar = 200 μm. (E) The protein expression of NE and MPO in neutrophils extracted from peripheral blood. (F) Representative immunofluorescence images staining for MPO (green), NE (red), and DAPI (blue) of neutrophils extracted from peripheral blood, scale bar = 100 μm
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