P011 Analysis of Innate-like Lymphocyte Subsets in Ulcerative Colitis
K. Haga*1, A. Chiba2, T. Shibuya1, T. Osada1, D. Ishikawa1, T. Kodani1, O. Nomura1, S. Watanabe1, S. Miyake2
1Juntendo University, Department of Gastroenterology, Tokyo, Japan, 2Juntendo University, Department of Immunology, Tokyo, Japan
Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory disorder of the large intestine. Recent studies have found that the failure of the immune tolerance towards the enteric bacteria or auto-antigens is one major pathogenic mechanism for the immune disorder in UC, but other aetiologic factors are yet to be identified. Innate-like lymphocytes are members of the lymphoid lineage that have emerging roles in mediating immune responses and regulating tissue homeostasis pertained to inflammatory bowel diseases (IBD) including Crohn's disease and UC. This study was to investigate the role of innate-like lymphocyte subsets in patients with UC.
A total of 36 UC patients and 34 age and gender matched healthy subjects were included in this study. Peripheral blood mononuclear cells (PBMC) were purified, and innate-like lymphocytes (MAIT cells, γδT cells, NK cells, iNKT cells, B-1 cells) were analysed by FACS LSR Fortessa with Flowjo software. Additionally, the production of cytokines including interleukin (IL)-17, IL-6, tumour necrosis factor (TNF)-α and interferon (IFN)-γ from each cell subsets, and activation markers were analysed by FACS. MAIT cells were identified as CD3+γδTCR-Vα7.2TCR+CD16 high cells, γδT cells as CD3+ γδTCR+ cells, iNKT cells as CD1d/PBS-57tetramer+CD3+cells, NK cells as CD3-CD56+cells, and B-1cells as CD19+CD20+CD27+CD43+cells.
In patients with UC, the frequency of MAIT cells and NK cells in the peripheral blood was significantly reduced as compared with healthy controls. The frequency of other innate-like lymphocytes such as γδT cells, iNKT cells, B-1cells showed no significant differences between patients and healthy individuals. The frequency of MAIT cells did not reflect the disease activity in UC patients, however there was a correlation between the activation marker for MAIT cells and the disease activity (measured by Mayo score). Further, MAIT cells from UC patients secreted more IL-17 than ells from healthy controls.
This study demonstrated that the activation marker expression for MAIT cells reflected UC disease activity. Mucosal associated invariant T (MAIT) cells are known as an innate-like lymphocyte phenotype, which exists in the mucosal tissue. The emergence of peripheral MAIT cells depends on the presence of commensal gut flora. Accordingly, MAIT cells could be involved in the pathogenesis of UC, and this study may suggest that the activation marker for MAIT cells may be a new biomarker for UC.