Research spotlight: researchers find a ‘switch’ in the gut for programming tolerance of inflammation

Roni Nowarski, PhD, of the Gene Lay Institute of Immunology and Inflammation and Department of Neurology, is the senior author of a paper published in Immunity.

What question were you investigating?

In inflammatory conditions, such as intestinal bowel disease, immune tolerance breaks down, leading to unresolved inflammation. Right now, we don’t have strategies to improve intestinal immune tolerance because there are gaps in our understanding of what stabilizes immune states within tissues and what makes them susceptible to inflammation. Our study explores an intestinal innate immune circuit that we think helps regulate immune tolerance.

What did you find?

We discovered a metabolic switch that, once turned on, can stabilize an immune-resistant state in intestinal macrophages and, therefore, confer protection against harmful intestinal inflammation.

What are the implications?

Our findings suggest that by activating a metabolic switch in the gut, we may be able to program immune tolerance to chronic inflammation and thereby promote maintenance of remission in inflammatory bowel disease patients.          

What excites you about this study?

We feel it’s an exciting story about how long-term tolerance to inflammation can be programmed in the gut by encoding a tissue-scale metabolic switch in macrophages.

Authorship: Randall T. Mertens, Aditya Misra, Peng Xiao, Seungbyn Baek, Joseph M. Rone, Davide Mangani, Kisha N. Sivanathan, Adedamola S. Arojojoye, Samuel G. Awuah, Insuk Lee, Guo-Ping Shi, Boryana Petrova, Jeannette R. Brook, Ana C. Anderson, Richard A. Flavell, Naama Kanarek, and Martin Hemberg.

Paper cited: Mertens RT et al. “A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance” Immunity DOI: 10.1016/j.immuni.2024.06.001