Intestinal mucosal function is injured in early phase of AP especially in patients with organ dysfunction, which may be a stimulus for development of multiple organ dysfunction and correlate with bad outcome in AP patients.

Sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains the leading complication for mortality caused by bacterial infection. The regulatory T (Treg) cells appear to be an important modulator in resolving lung injury. Despite the extensive studies, little is known about the role of macrophage HMGB1/PTEN/β-catenin signaling in Treg development during ALI. Objectives: This study was designed to determine the roles and molecular mechanisms of HMGB1/PTEN/β-catenin signaling in mediating CD4 + CD25 + Foxp3 + Treg development in sepsis-induced lung injury in mice. Setting: University laboratory research of First Affiliated Hospital of Anhui Medical University. Subjects: PTEN/β-catenin Loxp and myeloid-specific knockout mice. Interventions: Groups of PTEN loxp /β-catenin loxp and myeloid-specific PTEN/β-catenin knockout (PTEN M−KO /β-catenin M−KO ) mice were treated with LPS or recombinant HMGB1 (rHMGB1) to induce ALI. The effects of HMGB1-PTEN axis were further analyzed by in vitro co-cultures. Measures and Main Results: In a mouse model of ALI, blocking HMGB1 or myeloid-specific PTEN knockout (PTEN M−KO ) increased animal survival/body weight, reduced lung damage, increased TGF-β production, inhibited the expression of RORγt and IL-17, while promoting β-catenin signaling and increasing CD4 + CD25 + Foxp3 + Tregs in LPS- or rHMGB-induced lung injury. Notably, myeloid-specific β-catenin ablation (β-catenin M−KO ) resulted in reduced animal survival and increased lung injury, accompanied by reduced CD4 + CD25 + Foxp3 + Tregs in rHMGB-induced ALI. Furthermore, disruption of macrophage HMGB1/PTEN or activation of β-catenin significantly increased CD4 + CD25 + Foxp3 + Tregs in vitro . Conclusions: HMGB1/PTEN/β-catenin signaling is a novel pathway that regulates Treg development and provides a potential therapeutic target in sepsis-induced lung injury.

Incidences of Crohn disease (CD) have increased significantly in the last decade. Immunoproteomics are a promising method to identify biomarkers of different diseases. In the present study, we used immunoproteomics to study proteins of intestinal mucosal lesions and neighboring normal intestinal mucosa of 8 CD patients. Reactive proteins were validated by Western blotting. Approximately 50 protein spots localized in the 4 to 7 pI range were detected on two-dimensional electrophoresis gels, and 6 differentially expressed protein spots between 10 and 100 kDa were identified. Reactive proteins were identified as prohibitin, calreticulin, apolipoprotein A-I, intelectin-1, protein disulfide isomerase, and glutathione s-transferase Pi. Western blotting was conducted on the intestinal mucosa of another 4 CD patients to validate the reactive proteins. We found that intestinal mucosal lesions had high levels of prohibitin expression. Glutathione s-transferase expression was detected in 100% of the intestinal mucosa examined. Thus, we report 6 autoantigens of CD, including 3 new and 3 previously reported autoantigens. Intelectin-1, protein disulfide isomerase, and glutathione-s-transferases may be used as biomarkers for CD pathogenesis.