Ficolin‐A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis

• Published in: Immunology Vol. 151; no. 4; pp. 433 - 450
• Main Authors: Yang, Yi‐Fei, Zhou, Yi‐Dan, Hu, Jia‐Chen, Luo, Feng‐Ling, Xie, Yan, Shen, Yan‐Ying, Bian, Wen‐Xiu, Yin, Zhi‐Nan, Li, Hong‐Liang, Zhang, Xiao‐Lian
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2017; John Wiley and Sons Inc
• Subjects: Animals; Carbon tetrachloride; CCL4 protein; Cell Differentiation; Cells, Cultured; Chemokines; Colitis; Colitis - immunology; Complement Pathway, Mannose-Binding Lectin - genetics; Cytokines; Cytokines - metabolism; Damage; Dextran; Ficolins; ficolin‐2; ficolin‐A; Humans; Infectious diseases; Inflammation - immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory response; Interleukin 1; Interleukin 10; Interleukin 6; Intestine; Lectins - genetics; Lectins - metabolism; macrophage; Macrophage Activation; Macrophages; Macrophages - immunology; MAP kinase; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; MyD88 protein; NF-κB protein; Original; Pathogenesis; Patients; Polarization; Rodents; Signal Transduction; Signaling; Sodium; Sulfates; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Toll‐like receptor 4; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors; macrophage; ficolin-2; ficolin-A; inflammatory bowel disease; Toll-like receptor 4
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12741

Summary Human ficolin‐2 (FCN‐2) and mouse ficolin‐A (FCN‐A, a ficolin‐2‐like molecule in mouse) are activators of the lectin complement pathway, present in normal plasma and usually associated with infectious diseases, but little is known about the role of FCN‐A/2 in inflammatory bowel disease (IBD). In our present study, we found that patients with IBD exhibited much higher serum FCN‐2 levels than healthy controls. In the dextran sulphate sodium‐induced acute colitis mouse model, FCN‐A knockout mice showed much milder disease symptoms with less histological damage, lower expression levels of pro‐inflammatory cytokines [interleukin‐6 (IL‐6), IL‐1β and tumour necrosis factor‐α (TNF‐α)], chemokines (CXCL1/2/10 and CCL4) and higher levels of the anti‐inflammatory cytokine IL‐10 compared with wild‐type mice. We demonstrated that FCN‐A/2 exacerbated the inflammatory pathogenesis of IBD by stimulating M1 polarization through the TLR4/MyD88/MAPK/NF‐κB signalling pathway in macrophages. Hence, our data suggest that FCN‐A/2 may be used as a novel therapeutic target for IBD. Ficolin‐A knockout mice showed much milder colitis symptoms compared with wild‐type mice. Ficolin‐A/2 can aggravate the development of dextran sulphate sodium ‐induced colitis.