Project description:UNITI-2 was a phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT01369342) comparing the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.
Project description:Etrolizumab is an investigational monoclonal antibody that binds the β7 subunit of α4β7 and αEβ7 integrins. The relative contribution of α4β7 and αEβ7 to gut lymphocyte trafficking remains to be characterized. Here we show that αEβ7 is highly expressed on human intestinal CD8+ cytotoxic intraepithelial lymphocytes (IELs) and a small subset of proinflammatory CD4+ T cells. Dual blockade of α4β7 and αEβ7 reduced CD8+ T cell accumulation in the gut to a greater extent than single blockade of either pathway using a photo-convertible mouse model. αEβ7 blockade decreased T cell-epithelial interactions, increased the migratory speed and promoted egress of activated T cells. In Crohn’s disease patients treated with etrolizumab, a reduction of inflammatory genes and cytotoxic IEL gene signatures was observed. Concurrent blockade of α4β7 and αEβ7 increases reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of cell migration and tissue retention. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.
Project description:This study investigates the presence of specific fibrosis-associated gene expression signatures in Crohn's disease patient biopsies.
Project description:To investigate the gene expression profile of inflamed and non-inflamed mucosa in patients with Crohn's disease. To investigate TCR repertoires in the intestinal mucosa, the expression profile of the TCR repertoire gene was analyzed.
Project description:In Crohn's disease, creeping fat is the characteristic expansion of mesenteric adipose tissue wrapping around the inflamed intestine. Through a comparative transcriptomic analysis of creeping fat and normal-looking mesenteric adipose tissues from patients with Crohn's disease and non-Crohn's disease, we found that a dynamic transcriptional and cell compositional change occurs during the progression from non-Crohn's disease to Crohn's disease, and finally to creeping fat.