Interleukin-34 {-} a new modulator of human and experimental inflammatory bowel disease

Inflammatory bowel diseases (IBD), where Crohn’s disease (CD) and ulcerative colitis (UC) represent the two main forms, are chronic inflammatory conditions of the intestine. Macrophages play a central role for IBD pathogenesis and are regulated by major differentiation factors such as colony-stimulating factor 1 (CSF-1) in homeostasis and inflammation. Interleukin (IL)-34 has recently been discovered as a second ligand for the CSF-1 receptor (CSF-1R). However, expression and involvement of IL-34 in IBD remain unknown. Here, we investigated the expression of IL34, CSF1, and their shared receptor CSF1R in normal human ileum and colon, in inflamed and non-inflamed tissues of CD and UC patients, and in a mouse model of experimental colitis. We found distinct expression patterns of IL34 and CSF1 in ileum and colon, with higher IL34 in ileum and, on the contrary, higher CSF1 in colon. Further, IL34 and CSF1 expression was increased with inflammation in IBD patients and in experimental colitis. In humans, infiltrating cells of the lamina propria and intestinal epithelial cells expressed IL-34, and TNF-α regulated IL-34 expression in intestinal epithelial cells through the NF-κΒ pathway. These data demonstrate the expression pattern of IL-34 in ileum and colon and suggest IL-34 as a new modulator of inflammation in IBD.
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research