Altered expression of Butyrophilin ( <i>BTN</i> ) and BTN‐like ( <i>BTNL</i> ) genes in intestinal inflammation and colon cancer

Abstract

Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine <i>BTN</i> and <i>BTNL</i> genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human <i>BTN</i> and <i>BTNL</i> genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine <i>Btn</i> and <i>Btnl</i> genes was examined in mouse models of spontaneous colitis (<i>Muc2</i>^-/-) and intestinal tumorigenesis (<i>Apc</i>^Min/+). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially <i>BTN1A1</i>, <i>BTN2A2</i>, <i>BTN3A3</i>, and <i>BTNL8</i> were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of <i>BTNL2</i>, <i>BTNL3</i>, <i>BTNL8</i>, and <i>BTNL9</i> as compared to unaffected tissue. Colonic inflammation in <i>Muc2</i>^-/- mice significantly down-regulated the expression of particularly <i>Btnl1</i>, <i>Btnl4</i>, and <i>Btnl6</i> mRNA, and intestinal polyps derived from <i>Apc</i>^Min/+ mice displayed altered levels of <i>Btn1a1</i>, <i>Btn2a2</i>, and <i>Btnl1</i> transcripts. Thus, our data present an association of <i>BTN</i> and <i>BTNL</i> genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.