Oral administration of human carbonic anhydrase I suppresses colitis in a murine inflammatory bowel disease model

The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (ROR gamma t) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-gamma) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD.

Automated summary

The incidence of inflammatory bowel disease (IBD) is increasing, and effective treatments are needed. This study investigated the therapeutic effect of human carbonic anhydrase I (hCA I) in IBD and found that oral administration of hCA I significantly ameliorated colitis and induced immune tolerance, suggesting it as a potential new treatment option for IBD.