Scientists have made new discoveries about a protein involved in graft versus host disease. The protein, NLRP6, appears to have the opposite effect in graft versus host disease (GvHD) to its role in inflammatory bowel disease.
Dr Pavan Reddy of the University of Michigan, USA, and colleagues explain that NLRP6 regulates innate immune responses and the gastrointestinal environment. It is known to protect against ulcerative colitis, as well as the development of cancer.
The team looked at NLRP6’s role in gastrointestinal GvHD, a complication of allogeneic bone marrow transplant with similar symptoms to ulcerative colitis. However, in contrast to its role protecting against colitis, they found in mouse studies that NLRP6 aggravated the GvHD, which was independent of the gut microbiome.
“Our results unveil an unexpected, pathogenic role for host NLRP6 in gastrointestinal graft versus host disease that is independent of variations in the intestinal microbiome and in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis,” they report in the journal Nature Microbiology.
Dr Reddy said: “There are a lot of reasons NLRP6 seemed to work well in those other diseases, but in the case of graft versus host disease, it seemed to do the opposite.
“In mice where we knocked out NLRP6, instead of doing worse, they did better. That was a big surprise.”
Dr Hideaki Fujiwara, co-first author with Drs Tomomi Toubai and Corinne Rossi, added: “The composition of the microbiome does not seem to matter, unlike with other disease processes.”
The team suggest that the trigger for these opposing effects may be the compound taurine, which can be overproduced due to changes in the microbiome, signalling NLRP6, and leading to GvHD.
Blocking NLRP6 could be a possible route to preventing intestinal GvHD, they conclude.
Toubai, T., Fujiwara, H., Rossi, C., Riwes, M., Tamaki, H., Zajac, C., Liu, C., Mathew, A.V., Byun, J., Oravecz-Wilson, K., Matsuda, I., Sun, Y., Peltier, D., Wu, J., Chen, J., Seregin, S., Henig, I., Kim, S., Brabbs, S., Pennathur, S., Chen, G., Reddy, P. (2019) “Host NLRP6 exacerbates graft-versus-host disease independent of gut microbial composition”, Nature Microbiology, available at doi: 10.1038/s41564-019-0373-1