Early Involvement of Liver Natural Killer T Cells in Limiting Colonic Inflammation and Application to Disease Treatment

Abstract

Background and aims: Ulcerative colitis (UC) is chronic relapsing-remitting disease. Whereas it has been well characterized how various drug induce remission, the mechanisms involved in relapse are not known. We have previously shown that the epithelial expression of SOCS3, a negative regulator of cytokine signaling, was persistently upregulated in both active and inactive UC. Since the expression of SOCS3 during inactive disease may make the epithelial cells more vulnerable to various insults, we investigated whether this expression during remission was associated with the time till relapse. Materials and methods: 41 chronic UC patients in clinical remission underwent a first surveillance colonoscopy between 20012004, and were followed up till 2010. Biopsies from the first surveillance colonoscopy after remission were stained for SOCS3 protein expression and scored according to percentage of positive epithelial cells. Only biopsies from patients with clinical remission and without signs of histological inflammation were included. Clinical data, endoscopy and histology reviews were collected from patient charts. Results: 23 Patients (57.0%) of the 41 chronic UC patients developed histological relapse, and 19 patients (46.3%) had endoscopic relapse of colitis during the course of surveillance. SOCS3 protein expression in colon biopsies of inactive UC patients had a negative correlation with the time till histological (p<0.001) and endoscopic (p=0.007) relapse. Patients with higher epithelial SOCS3 expression at early remission suffered from a significantly more severe colitis during relapse (p=0.001). There was no correlation with CRP levels. Conclusion: Here we found that high levels SOCS3 expression in epithelial cells during remission was associated with a shorter time till relapse and increased severity of inflammation during relapse. These data further strengthen our hypothesis that SOCS3 expression may contribute to enhanced vulnerability of the intestinal epithelial cells during remission. As such, the dynamic changes and the mechanisms involved in this SOCS3 expression during mucosal remission will be further investigated.