Fig 1: Targeting gut IEL-primed neutrophils to attenuate proinflammatory gut-liver crosstalk. In the course of intestinal inflammation, neutrophils interact with IELs via CD112, leading to enhanced NETosis. Neutrophils that undergo NET formation migrate from the intestine to the liver, contributing to secondary liver injury. The CD112-derived peptide DPX2 inhibits neutrophil priming by IELs and attenuates the proinflammatory gut-liver crosstalk
Fig 2: CD112-derived peptide DPX2 disrupts CD112–CD226 interaction and attenuates IEL-induced NETs. (A) Flow cytometric analysis of CD112-expressing neutrophils isolated from the whole intestinal epithelium of sham and gut I/R mice (n = 4 per group). The Student’s t-test was applied. *p < .05 versus sham. (B) The CD112 sequence, with highlighting residues 249–261 of CD112, was used to design DPX2 (RYPPEVSISGYDD). (C) Docking model and surface interaction view showing predicted binding of DPX2 to CD226. (D) Computing models of interaction between CD112 and CD226 with/without DPX2. (E) Surface plasmon resonance (SPR) analysis demonstrating that DPX2 competitively inhibits CD112–CD226 binding. Representative sensorgrams are shown. (F, G) Neutrophils were cultured with IELs with PBS, a scrambled peptide (Scr.), or DPX2 under hypoxia/reoxygenation (F) or in the presence of LPS (G) (n = 6 per group). ANOVA was used for one-way comparison among multiple groups, and the significance was determined by the Tukey method. *p < .05 versus PBS, #p < .05 versus Scr. H/R, hypoxia/reoxygenation
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