Interleukin-34 sustains inflammatory pathways in the gut

IBD (inflammatory bowel disease)-related tissue damage occurs in areas which are massively infiltrated with monocytes/macrophages. These cells respond to inflammatory stimuli with enhanced production of cytokines/chemokines. In the present study, we analysed the expression and role of IL (interleukin)-34, a regulator of monocyte/macrophage differentiation, survival and function, in IBD. A significant increase in IL-34 mRNA and protein expression was seen in inflamed mucosa of patients with CD (Crohn's disease) and patients with UC (ulcerative colitis) compared with the uninvolved areas of the same patients and normal controls. IL-34 was up-regulated in LPMCs (lamina propria mononuclear cells) isolated from normal colon by TNF-alpha (tumour necrosis factor alpha) and TLR (Toll-like receptor) ligands and was down-regulated in intestinal biopsies and LPMCs of IBD patients upon treatment with infliximab. Treatment of normal LPMCs with IL-34 increased TNF-alpha expression in an ERK1/2 (extracellular-signal-regulated kinase 1/2)-dependent fashion and neutralization of IL-34 in IBD mucosal explants reduced TNF-alpha and IL-6 synthesis. In conclusion, our results indicate that IL-34 is up-regulated in IBD and suggest a role for this cytokine in sustaining the inflammatory responses in this disease.