CCR6 Deficiency Aggravates Colitis in a Spontaneous Mouse Model of Colitis

Introduction/background: Chemokine receptor 6 (CCR6) is expressed by both pro-inflammatory cells and regulatory T cells and its ligand CCL20 is predominantly expressed by intestinal epithelial cells.  CCR6/CCL20 axis is implicated to play a major role in the pathogenesis of IBD. The CCR6/CCL20 axis is paradoxical as it is involved in both immune regulation and activation. The contradictory role of CCR6/CCL20 in inflammation/intestinal homeostasis requires further investigation in a relevant spontaneous model of colitis.   

Aim: To assess the role of CCR6 in an inflammatory environment of spontaneous colitis model Winnie, with established colitis.

Methods: CCR6 deficient Winnies were generated and assessed with clinical, histological& immunological parameters.

Results: Clinical parameters showed significant increase in the colon weight/body weight in CCR6 deficient Winnie mice compared to sex and age matched controls. Histological examinations revealed the aggravated colitis specifically in mid to proximal colon region. Immuno-phenotyping of colonic lymphocytes indicated reduction in the Fox P3+ Tregs and increased Th17 cells.

Discussion/conclusion: Our studies indicate that CCR6 deficiency aggravates colitis in an established chronic colitis setting.  Further detailed mechanism of CCR6 function will provide an insight in understanding of CCR6/CCL20 in the pathogenesis of IBD.