Research ArticleSystems Biology

An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease

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Science Signaling  04 Aug 2020:
Vol. 13, Issue 643, eaay3258
DOI: 10.1126/scisignal.aay3258

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Found in translation

An ongoing challenge for the development of new therapeutics is the difficulty in translating findings from preclinical animal models to human subjects, more so when different types of data (proteomics versus transcriptomics) are compared. Brubaker et al. developed a method to project transcriptomic data from patients with inflammatory bowel disease (IBD) into a principal components analysis of mouse proteomics data to investigate resistance to the anti-TNF antibody infliximab. This analysis, which suggested that integrin signaling contributed to resistance, was validated in experiments, showing that inhibiting α1 integrin subunit signaling enhanced the ability of infliximab to suppress proinflammatory cytokine release from immune cells. These data suggest that this approach for comparing model system and patient data might reveal therapeutically relevant targets for other diseases.

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