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Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A in linking tissue homeostasis and intestinal inflammation is not known. Here, using cell-specific genetic deletion models, we report an essential role for CX3CR1+ mononuclear phagocyte (MNP)-derived TL1A, which is induced by adherent IBD-associated microbiota, in regulating group 3 innate lymphoid cell (ILC3) production of IL-22 and mucosal healing in acute colitis. However, in contrast to this protective role in acute colitis, TL1A-dependent expression of OX40L in MHCII+ ILC3 during colitis leads to co-stimulation of antigen-specific T cells and is required for chronic T cell colitis. These results identify a new role for ILC3 in regulating intestinal T cells and reveal a central role for TL1A in regulating ILC3 barrier immunity during colitis. Overall design: RNA from media- or TL1A-stimulated sorted Lin-CD127+IL23R-GFP+ ILC3s from IL23R-GFP/WT mice</long_description><tag>xref:PubMed:30552020</tag><repository>ENA</repository></additional><is_claimable>false</is_claimable><name>TL1A is a central regulator of group 3 innate lymphoid cell function in colitis</name><description>TL1A is a central regulator of group 3 innate lymphoid cell function in colitis</description><dates><last_updated>2025-09-24</last_updated><first_public>2019-01-03</first_public></dates><accession>PRJNA494250</accession><cross_references><GEO>GSE120723</GEO><taxon>10090</taxon><PubMed>30552020</PubMed></cross_references></HashMap>