Loss of Acid Ceramidase in Myeloid Cells Protects from Chronic Colitis in IL10-Deficent Mice

<b>BACKGROUND AND CONTEXT:</b> Acid ceramidase expression is increased in immune cells in patients with inflammatory bowel disease, specifically in macrophages.<b>NEW FINDINGS:</b> We determined that loss of acid ceramidase (AC) in macrophages, but not neutrophils, impairs inflammatory functions <i>in vitro,</i> and that loss of AC in myeloid cells partially protects from spontaneous colitis <i>in vivo</i> by reducing immune cell recruitment into intestinal tissue. <b>LIMITATIONS:</b> The IL10 knockout model of colitis exhibits highly variable onset and severity of disease, which may be challenging to distinguish the extent of protection.<b>CLINICAL RESEARCH RELEVENCE:</b> This study identifies AC as a promising therapeutic target for treating inflammatory bowel disease.<b>BASIC RESEARCH RELEVENCE:</b> This study contributes to our understanding of the role that AC plays in inflammation within immune cells, specifically myeloid cells. Additionally, this study underscores the role of immune cell sphingolipid metabolism in inflammatory bowel disease.<b>LAY SUMMARY:</b> Loss of acid ceramidase in myeloid cells protects from chronic colitis by decreasing inflammation, altering immune cell function, and impairing the recruitment of effector immune cells to the colon.