Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease
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Research from the University of Tsukuba explains how an experimental drug for inflammatory bowel disease works, but it was not in the way that researchers expected.
E6007 is an experimental therapy being evaluated in Japan for patients with ulcerative colitis. In mouse models of the condition, immune cells stick to the wall of the gut, leading to inflammation. E6007 was thought to block cell adhesion receptors known as integrins — but that outcome turns out to be an indirect effect.
The study authors showed that a molecule very similar to E6007 binds to a particular ‘chaperone’ protein called calreticulin, which interferes the binding of an integrin subunit. Without this interaction, immune cells cannot stick as well to cells along the gut.
The findings offer additional scientific rationale for clinically developing E6007, which is thought to share the same mechanism of action.
- Nature Communications 9, 1982 (2018). doi: 10.1038/s41467-018-04420-4
|Eisai Co., Ltd., Japan||0.38|
|Tokuyama Corporation, Japan||0.38|
|University of Tsukuba, Japan||0.24|
|EA Pharma Co., Ltd., Japan||0.01|