Restored Macrophage Function Ameliorates Disease Pathophysiology in a Mouse Model for IL10 Receptor-deficient Very Early Onset Inflammatory Bowel Disease.

ABSTRACT:

Background and aims

Mutations in IL10 or the IL10 receptor lead to very early onset [VEO] inflammatory bowel disease [IBD], a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signalling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD.

Methods and results

We here evaluated haematopoietic stem cell gene therapy in a VEO-IBD mouse model and demonstrated that the therapeutic response closely co

SUBMITTER: Ackermann M 

PROVIDER: S-EPMC8464221 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature