A New Clue to Why Celiac Disease Develops: lnc13

Why do most people tolerate gluten while others develop celiac disease?

A new study published in Nature Immunology points to a possible answer. Researchers found that a long noncoding RNA called lnc13 helps keep inflammatory immune responses to gluten in check, and that loss of this protective mechanism can trigger celiac disease-like changes in genetically susceptible mice.

Celiac disease develops when the immune system mounts an inappropriate response to gluten, leading to inflammation and damage in the small intestine. Although scientists have identified many of the genetic and immune factors involved, the mechanisms that normally maintain tolerance to gluten remain incompletely understood. To investigate this question, researchers focused on lnc13, a molecule previously linked to celiac disease risk that helps regulate the activity of other genes.

Using genetically modified mice carrying the human HLA-DQ8 risk gene, researchers found that animals lacking lnc13 developed many features that resemble celiac disease after exposure to gluten. These included increased inflammatory immune activity, expansion of cytotoxic immune cells in the intestine, production of celiac-associated antibodies, and structural changes in the small intestine consistent with early disease. Importantly, many of these changes improved when gluten was removed from the diet.

The study also identified a possible mechanism behind these effects. The researchers found that lnc13 helps limit the activity of IL-15, an immune signaling molecule long recognized as an important driver of celiac disease. Without lnc13, immune cells became more responsive to IL-15 and were more likely to develop into inflammatory, tissue-damaging cells. 

Because celiac disease is one of the few autoimmune diseases with a known environmental trigger, researchers believe it offers a valuable model for understanding how immune tolerance breaks down. While additional studies will be needed to determine whether lnc13 could eventually become a therapeutic target, the findings provide new insight into the molecular mechanisms that normally help prevent harmful immune responses to food. 

Related: In March 2026, co-author Dr. Arnold Han discussed how advances in immune profiling technologies are helping researchers better understand the cellular events that drive celiac disease and how those discoveries may inform research into autoimmune diseases more broadly during the 100th episode of Beyond Celiac’s Celiac Straight Talk podcast: Unlocking Autoimmunity Through Celiac Research.

Citation

Yang-Fischer, R., Shearer, A., Leão, F.B. et al. The long noncoding RNA lnc13 restrains inflammatory responses to maintain oral tolerance to gluten. Nat Immunol 27, 1145–1158 (2026). https://doi.org/10.1038/s41590-026-02506-6