Scientists block immune signal to reduce gut inflammation
Updated
Updated · SciTechDaily · May 6
Scientists block immune signal to reduce gut inflammation
7 articles · Updated · SciTechDaily · May 6
Weill Cornell Medicine researchers reported in the Journal of Experimental Medicine that blocking “Signal Two” increased gut RORγt+ regulatory T cells and protected against intestinal inflammation in a preclinical model.
The finding overturns assumptions that this second immune signal is needed to expand tolerance-enforcing cells in the intestine, suggesting new strategies for inflammatory bowel disease, food allergies and other autoimmune disorders.
The team said the work may explain why abatacept failed in a 2012 IBD report: patients may lack key RORγt+ antigen-presenting cells needed for the treatment to work.
How does silencing an immune 'go' signal in the gut paradoxically teach the body tolerance?
Can we manipulate the gut's unique immune rules to prevent food allergies and other inflammatory disorders?
Restoring Gut Immune Balance: The Role of RORγt+ APCs and Abatacept in Inflammatory Bowel Disease
Overview
In May 2026, Weill Cornell researchers discovered that blocking the co-stimulatory Signal Two with abatacept in the gut unexpectedly expands a special group of regulatory T cells (RORγt+ Tregs) that maintain immune tolerance to food and gut bacteria. This expansion depends on antigen presentation (Signal One) by RORγt+ antigen-presenting cells (APCs), which are often depleted during active inflammatory bowel disease (IBD), explaining why past abatacept trials failed. New strategies propose using abatacept during remission or alongside therapies that restore these APCs. Preclinical models show abatacept reduces gut inflammation, and its favorable safety profile supports its potential as a targeted treatment to restore gut immune balance.