Long-lived Yolk-sac Derived Intestinal Macrophages Interact with Submucosal and Myenteric Neurons

status: publishe

Long-Lived Yolk-Sac Derived Macrophages Interact with Myenteric and Submucosal Neurons

status: publishe

Intestinal resident macrophages prune synapses of enteric neurons during development

status: publishe

Biopsy-derived intestinal epithelial cell cultures for pathway based stratification of patients with inflammatory bowel disease

Endoplasmic reticulum stress was shown to be pivotal in the pathogenesis of inflammatory bowel disease. Despite progress in IBD drug development, not more than one third of patients achieve steroid-free remission and mucosal healing with current therapies. Furthermore, patient stratification tools for therapy selection are lacking. We aimed to identify and quantify epithelial ER stress in a patient-specific manner in an attempt towards personalized therapy.status: publishe

Strong Upregulation of AIM2 and IFI16 Inflammasomes in the Mucosa of Patients with Active Inflammatory Bowel Disease

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut, partly driven by defects in the innate immune system. Considering the central role of inflammasome signaling in innate immunity, we studied inflammasome components in IBD mucosa. METHODS: Expression of genes encoding inflammasome sensor subunits was investigated in colonic mucosal biopsies from 2 cohorts of patients with IBD and controls. RESULTS: A significant upregulation (>2-fold change in expression, false discovery rate <0.05) of the PYHIN inflammasomes AIM2 and IFI16 in active IBD versus controls was found. Also IFI16 was significantly increased in inactive IBD versus controls. Moreover, responders to anti-tumor necrosis factor therapy showed decreased expression of these inflammasomes although IFI16 remained significantly increased in responders showing endoscopic healing versus controls. AIM2 was mainly expressed in epithelial cells, whereas IFI16 was expressed in both lymphocytes and epithelial cells. Functional activation of predominant AIM2/IFI16-mediated inflammasomes in active IBD colon was shown by the presence of the downstream effectors CASP1 and HMGB-1 in inflamed mucosa. CONCLUSIONS: Our results highlight the importance of PYHIN inflammasome signaling in IBD and also link anti-tumor necrosis factor responsiveness to inflammasome signaling. Together, this points to the potential value of the inflammasome pathway as a new therapeutic target for IBD treatment.status: publishe