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

Abstract

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.

Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation

“…[10][11][12] Imbalance of M1/M2 macrophage polarization contributes to the occurrence and development of IBD. [13][14][15][16][17] Previous studies have proved that macrophages massively accumulated in the inflamed colon tissue and M1 phenotype was predominant in IBD patients. 18 Moreover, Kawano and colleagues reported that short-term high-fat diet could increase the number of pro-inflammatory macrophages in the lamina propria of colon, accompanied by increased expression levels of proinflammatory cytokines such as TNF-α and IL-1β, which highlighted the critical role of M1 macrophages in the HFD-related colonic inflammation.…”

Mannose‐capped lipoarabinomannan‐induced B10 cells decrease severity of dextran sodium sulphate‐induced inflammatory bowel disease in mice

“…To assess the effects of the ManLAM‐induced B10 cells on murine IBD, ManLAM‐treated B cells (labelled with CFSE) were adoptively transferred into IL‐10 −/− mice (6 mice per group) on Day 3. The IL‐10 −/− mice were fed with 3% (w/v) DSS (#SKU 0216011080, MP Biomedicals, LCC, Solon, OH) in drinking water from Day 0 to Day 7, and then were followed by tap water as previously described . The body weight of mice was measured every day.…”

Neutralization of IL‐10 produced by B cells promotes protective immunity during persistent HCV infection in humanized mice

“…Liver tissues were fixed in 4% paraformaldehyde, embedded in paraffin and sectioned (5 μm) for HE and Masson's trichrome staining. The immunohistochemistry (IHC) assay were performed as described elsewhere [16,40] using primary antibody anti-NS3 (Abcam) and peroxidase-labelled rabbit anti-mouse IgG (Servicebio, Woburn, USA). Immunofluorescence staining was performed as described previously [39]; frozen sections of liver tissue (4 μm) were fixed and blocked, and then stained with anti-CD19 (Servicebio) and anti-IL-10 antibody (Absin Bioscience Inc., Shanghai, China).…”