SPECIFIC immune cells in the large intestine are moved by cholesterol metabolites, a process which underpins the formation of lymphoid tissue in the intestine, according to a study conducted by scientists at the Karolinska Institutet, Solna, Sweden. The findings have identified a potential therapeutic target for inflammatory bowel disease.
Forming Lymphoid Tissue
The team discovered that cholesterol metabolites, called oxysterols, stimulate innate lymphoid cells (ILCs) in the large intestine to form the immune system’s important lymphoid tissue, regardless of whether or not inflammatory bowel disease exists. In patients who have autoimmune inflammatory bowel disease, such as ulcerative colitis, chronic inflammation can be caused by the lymphoid tissue reacting to the body’s own cells. Therefore, understanding how lymphoid tissue is created could help establish therapeutic pathways for patients with the condition.
“We have discovered that ILCs use a surface protein called GPR183 to sense the oxysterols, which attracts ILCs to specific sites in the large intestine where lymphoid tissue is formed,” explained Dr Tim Willinger, Karolinska Institutet. “Our findings are relevant to humans because inflammatory lymphoid tissue contributes to tissue damage in inflammatory bowel disease. We have discovered that patients with ulcerative colitis have higher levels of oxysterol-producing enzymes than healthy controls. The results indicate that oxysterols and GPR183 are involved in ulcerative colitis.”
Drug Development
The researchers therefore believe that attempting to inhibit GPR183 or oxysterol production could be a target for drug development in inflammatory bowel disease. Finding novel ways to treat this common and severe condition is crucial, as no cure currently exists.
James Coker, Reporter
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