Innate lymphoid cells activated by the cytokine TL1A link colitis to emergency granulopoiesis and the recruitment of tumor-promoting neutrophils.
| Publication Type | Academic Article |
| Authors | Pires S, Yang W, Frigerio S, Louis C, Scott C, Zhou Y, Cardakli E, Tran N, Hassan-Zahraee M, Ye Z, Hyde C, Hung K, Chen A, Ng C, Grier A, Lukin D, Scherl E, Targan S, Diehl G, Grootjans J, Putoczki T, Wicks I, Longman R |
| Journal | Immunity |
| Volume | 59 |
| Issue | 2 |
| Pagination | 372-387.e7 |
| Date Published | 01/22/2026 |
| ISSN | 1097-4180 |
| Keywords | Tumor Necrosis Factor Ligand Superfamily Member 15, Neutrophils, Colitis, Lymphocytes, Granulocytes, Colorectal Neoplasms |
| Abstract | Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Genetic variants in TNFSF15, encoding tumor necrosis factor (TNF)-like cytokine 1A (TL1A), associate with severe IBD and advanced CRC. Here, we investigated how TL1A signaling promotes colitis-associated tumorigenesis. Deletion of the TL1A receptor in tissue-resident type 3 innate lymphoid cells (ILC3s) reduced colitis-associated tumorigenesis. TL1A signaling promoted neutrophil recruitment to the colon, which was required for tumor development. TL1A-stimulated ILC3s activated neutrophils, inducing a tumor-associated neutrophil (TAN)-like gene signature, and transfer of these neutrophils was sufficient to promote tumor growth. A similar TAN-like gene signature was enriched in human colitis-associated dysplasia but reduced following TL1A blockade in ulcerative colitis patients. Mechanistically, TL1A and colitis triggered emergency granulopoiesis, expanding granulocyte-monocyte progenitors and neutrophils in a manner dependent on ILC3-derived granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, a TL1A-ILC3-GM-CSF axis links colitis with emergency granulopoiesis and may serve as a therapeutic target to reduce colitis-associated CRC. |
| DOI | 10.1016/j.immuni.2025.12.008 |
| PubMed ID | 41576959 |
| PubMed Central ID | PMC12981380 |