Interleukin-19 is a negative regulator in TNBS-induced experimental colitis

抄録

Background: IL-19 was originally found by sequence homology to IL-10, and is a member of the IL-10 family, which includes IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29. However, little is known about the exact immunological role of IL-19 in the regulation of inflammatory bowel disease (IBD) that is characterized by dysregulated intestinal inflammation and mucosal tissue damage in parts of the gastrointestinal tract. Clinically, ulcerative colitis and Crohns disease (CD) are two of the most common types of IBDs. CD is characterized by transmural and discontinuous inflammation, which is associated with a Th1 response mainly driven by IL-12 and IFN-gamma. In this study, we investigated the role of IL-19 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis which is useful for the study of the Th1 inflammatory response and resembles the symptom seen in CD.

Methods: Balb/c genetic background IL-19 knockout (KO) mice were used. TNBS was prepared in a 50% ethanol solution at a final concentration of 25 mg/mL. Colitis was induced by intrarectal administration with 100 μL of TNBS solution using a plastic catheter. The colitis was evaluated by analyzing body weight loss, histology, and cytokine expression of the distal colon.

Results: IL-19 KO mice exhibited severe weight loss compared with wild-type (WT) mice from day 2 to day 4. Histological analysis revealed that the distal colons of IL-19 KO mice contained more infiltrating cells than those of WT mice, particularly for transmural infiltration, and extensive damage to both goblet and epithelial cells was observed 3 days after TNBS administration. The distal colon of IL-19 KO mice contained a high level of F4/80 positive cells and dramatically increased infiltration of plasma cells. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of IFN-gamma, IL-12, IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5.

Conclusions: In this study, our experiments highlighted several novel aspects of the anti-inflammatory effects of IL-19 in TNBS-induced colonic inflammation in vivo.