Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn's disease recurrence.

ABSTRACT:

Objective

Reduced Paneth cell (PC) numbers are observed in inflammatory bowel diseases and impaired PC function contributes to the ileal pathogenesis of Crohn's disease (CD). PCs reside in proximity to Lgr5⁺ intestinal stem cells (ISC) and mitochondria are critical for ISC-renewal and differentiation. Here, we characterise ISC and PC appearance under inflammatory conditions and describe the role of mitochondrial function for ISC niche-maintenance.

Design

Ileal tissue samples from patients with CD, mouse models for mitochondrial dysfunction (Hsp60^Δ/ΔISC) and CD-like ileitis (TNF^ΔARE), and intestinal organoids were used to characterise PCs and ISCs in relation to mitochondrial function.

Results

In patients with CD and TNF^ΔARE

SUBMITTER: Khaloian S 

PROVIDER: S-EPMC7569388 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature