Intestinal CD103+CD4+ and CD103+CD8+ T-Cell Subsets in the Gut of Inflammatory Bowel Disease Patients at Diagnosis and During Follow-up

Abstract

Background The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with β7 (Etrolizumab, anti-β7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103+T-cell subsets, both CD4+ and CD8+, in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. Methods Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103+ T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. Results In total, 75 Crohn’s disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103+T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103+CD4+ in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103+CD8+ compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103-CD4+ T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103+ and CD103-T-cell subsets were comparable with healthy controls. Conclusion At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103+CD4+ and CD103+CD8+T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103-T cells was observed during active inflammation.

Integrated Bioinformatics Analysis Identifies ELAVL1 and APP as Candidate Crucial Genes for Crohn’s Disease

“…Interestingly, the data of xCell indicated that CD4 + and CD8 + T cell proportions are obviously reduced in the blood, which may be caused by the increased migration of T cells into the gut and/or the exhaustion of T cells. Consistent with FACS data from other literatures [ 61 – 63 ], our xCell analysis highlight the decrease of CD8 + Tem as a general signature in the blood of CD, which is conventionally considered a cytotoxic cell type to defect the infection of virus. Although little is known about the detail mechanism, these phenomena suggest that the decrease of T cells, especially the CD8 + Tem, in the peripheral blood may be a novel feature for certain CD patients.…”

Waiting in the wings: RUNX3 reveals hidden depths of immune regulation with potential implications for inflammatory bowel disease

“…T‐bet bound within Runx3 loci of in vitro induced CD4 + CD8αα + IELs, promoted Runx3 expression and lead to CD103 upregulation 26 . A shift from a proinflammatory CD4 + CD103 + population towards CD103 − leucocytes occurred during active inflammation 28 . Comparison of newly diagnosed IBD cases and patients in remission showed higher abundance of CD103 − subpopulations in the gut of newly diagnosed individuals.…”

Total Recall: Intestinal TRM Cells in Health and Disease

“…Roosenboom and colleagues reported decreased numbers of CD103 + CD4 + and CD103 + CD8 + T cells in active IBD and found a rise of these numbers in the remission phase up to levels comparable with healthy controls. In addition, they observed a lower number of CD103 - T cells in healthy controls and IBD patients in remission in comparison with active CD and UC patients ( 65 ). Importantly, this study was not specifically designed to assess T RM cells.…”