Crohn's disease, a type of inflammatory bowel disease, is a condition that occurs when your body's immune system mistakenly attacks and destroys healthy body tissue. The exact cause of Crohn's disease is unknown.
A new report in the Journal of Leukocyte Biology shows for the first time precisely what type of immune cells are involved in driving the inflammation process in the disease. With this knowledge, new compounds can be identified which reduce the activity of these cells or lessen their inflammatory effects.
"By increasing the knowledge on the different macrophage subsets in the intestine and their blood counterparts, we hope to contribute to the discovery of more specific targets in Crohn's disease, increasing the efficiency of new treatments," said Olof Grip, M.D., Ph.D., a researcher involved in the work from the Department of Clinical Sciences Malmö, at Lund University in Malmö, Sweden.
To make this discovery, scientists studied blood and intestinal biopsy samples from healthy individuals and from people with Crohn's disease. They compared the proportions and specific characteristics of the cells between the two. The blood monocytes were classified into three different subsets, classical, intermediate and non-classical monocytes, and the intestinal macrophages into CD14hiHLA-DRdim, CD14hiHLA-Dbright and CD14loHLA-DRint. Researchers then purified these three subsets from the blood using advanced fluorescence-activated cell sorting techniques. Several functional properties of the purified cells were investigated by analyzing components that have been shown to be important in disease such as release of pro-inflammatory cytokines, matrix metalloproteinases and the ability of the monocytes to migrate toward CCL2.
In people with Crohn's disease the specific subset of CD14hiHLA-DRdim macrophages is increased while the resident macrophage population is unaltered. These CD14hiHLA-DRdim macrophages are most likely derived from recruited classical blood monocytes, which are the most pro-inflammatory.
This suggests that the CD14hiHLA-DRdim macrophages are driving the inflammation seen in Crohn's disease, exacerbating the inflammation and leading to tissue destruction.