C-C Motif Ligand 20 (CCL20) and C-C Motif Chemokine Receptor 6 (CCR6) in Human Peripheral Blood Mononuclear Cells: Dysregulated in Ulcerative Colitis and a Potential Role for CCL20 in IL-1\(\beta\) Release  
[PERSON]  
1 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; [EMAIL_ADDRESS] (H.K.S. ); [EMAIL_ADDRESS] (J.K.D. ); [EMAIL_ADDRESS] (A.v.B.G. ); [EMAIL_ADDRESS] (A.E.O. ); [EMAIL_ADDRESS] (B.D. ); [EMAIL_ADDRESS] (T.E.M.) 2 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway; [EMAIL_ADDRESS] (Department of Infectious Diseases, St. Olav's University Hospital, 7030 Trondheim, Norway (Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7030 Trondheim, Norway (Clinic of Medicine, St. Olav's University Hospital, 7030 Trondheim, Norway (Department of Immunology, Oslo University Hospital and University of Oslo, 0372 Oslo, Norway (Research Laboratory, Department of Laboratory Medicine, Nordland Hospital, 8005 Bodo, Norway (Research Laboratory, Department of Laboratory Medicine, Nordland Hospital, 8005 Bodo, Norway (Research Laboratory, Department of Laboratory Medicine, Nordland Hospital, 8005 Bodo, Norway (Research Laboratory  
view of the diseases is that inflammation occurs through an aberrant immune reaction to a normally tolerated gut flora in genetically susceptible individuals [1]. While many factors involved in driving a chronic inflammatory response have been identified, it is hitherto unknown what initiates the inflammation in IBD. The gastrointestinal mucosa has been established as an important constituent of the immune system due to its close contact with the microbiome [2] and the number of immune cells within the mucosa is higher in the gut than in other organs [3]. The balance between inflammatory response and tolerance towards gut flora depends on the proportions of regulatory and effector immune cells in the mucosa. Chemokines participate in the regulation of the immune cell composition, since cells expressing the corresponding receptor are directed towards the site of chemokine production (e.g., mucosal cells), along a concentration gradient [4; 5; 6]. CCL20 is a C-C motif chemokine ligand, which has C-C motif Chemokine Receptor 6 (CCR6) as its sole receptor [7; 8] and tissues producing CCL20 recruit CCR6 expressing immune cells [9; 10; 11; 12]. As CCL20 recruits both regulatory T cells and Th17 cells, a change in CCL20 expression can potentially alter the balance between proinflammatory and regulatory responses [13; 14; 15]. CCL20 is increased in the mucosa of IBD patients [16; 17; 18] and CCL20 and CCR6 have been identified as IBD susceptibility genes and are suggested as treatment targets in inflammatory conditions [19; 20]. Studies on CCL20 and CCR6 in mononuclear cells from circulation of patients with UC indicate that CCL20 mRNA is upregulated during active disease compared to healthy controls [21; 22; 23]. [PERSON] et al. proposed serum CCL20 as a potential biomarker for active CD [24]. We have previously found CCL20 expression in both the epithelium and in mononuclear cells in the lamina propria [18]. The activity of circulating immune cells is of interest during active inflammation. Indeed, the current hypothesis on the extraintstinal manifestations in IBD is that immune cells activated in the intestinal mucosa migrate to other organs and initiate inflammation [25; 26]. [PERSON] et al. identified expression patterns specific for IBD and rheumatoid arthritis in PBMCs, suggesting that new insights may be gained from studying patient mononuclear cells in inflammatory diseases [27]. The current understanding is that CCL20 is released mainly in response to other inflammatory cytokines, such as TNF and IL-1\(\beta\), indicating a role for CCL20 when inflammation is ongoing. However, the mechanisms behind CCL20 release from immune cells in IBD have not been thoroughly investigated.