Immune regulation by integrin-linked kinase (ILK) during intestinal inflammation

Lead researcher

Dr Afsar U Ahmed

Main finding

The main finding of this study is discovering the impact of the expression of integrin-linked kinase (ILK) in myeloid (innate immune) cells on driving inflammation in colonic epithelium. This finding further underscores the critical involvement of myeloid cells in intestinal homeostasis and inflammation, an emerging area where the mechanistic details are not completely understood. Through the identification of myeloid-ILK as a mediator of intestinal inflammation, this study not only uncovers a role for ILK in myeloid-to-epithelial signalling cascades, but also indicates a wider implication for integrin/adhesion signalling in myeloid cell biology. We show that targeting myeloid-ILK-dependent inflammatory signalling in the mucosal epithelium via pharmacological inhibition of ILK, highlights a novel therapeutic option for inflammatory bowel disease (IBD).

Centre

Centre for Cancer Research

Research group

Cancer and Innate Immunity

Co-authors

Howard CH Yim, Mariah Alorro, Matthias Ernst and Bryan RG Williams

Journal and article title

Most surprising

That the selective expression of ILK in the myeloid compartment had such a profound effect on the regulation of inflammatory signalling in the mucosal epithelium, leading to colonic epithelial injury during colitis was surprising. This novel finding establishes myeloid-ILK as a key driver of acute intestinal inflammation and pathology during experimental colitis.

Future implications

By revealing an important role of myeloid-ILK in intestinal inflammation, this study suggests that ILK inhibitors could be effective for the treatment of gut inflammation in patients with IBDs. Current evidence supports a causal role for myeloid cells in the pathogenesis of many diseases including IBDs, but the underlying mechanism is yet to be completely understood. This study also provides a step forward towards our current understanding of myeloid cell biology in intestinal inflammation.

Disease/health impact

Inflammatory bowel diseases (IBDs)

Other points of interest

Since innate immune signalling has been identified as a critical regulator of many pathological conditions over the last decade, this study further emphasizes the need for targeting immune regulation as a more accurate and effective therapeutic option.