Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis.

ABSTRACT

Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis. In particular, neutrophils are key effector cells and are first line defenders against invading pathogens. While the activity of neutrophils in the intestinal mucosa is required for homeostasis, regulatory mechanisms are equally important to prevent unnecessary activation. In ulcerative colitis, unregulated neutrophil inflammatory mechanisms promote tissue injury and loss of homeostasis. Aberrant neutrophil function represents an early checkpoint in the detrimental cycle of chronic intestinal inflammation; thus, dissecting the mechanisms by which these cells are regulated both before and during disease is essential for understanding the pathogenesis of ulcerative colitis. We present an analysis of the role of sphingolipids in the regulation of neutrophil function and the implication of this relationship in ulcerative colitis.