Innate lymphoid cells activated by the cytokine TL1A link colitis to emergency granulopoiesis and the recruitment of tumor-promoting neutrophils
- Author(s)
- Pires, S; Yang, W; Frigerio, S; Louis, C; Scott, C; Zhou, YL; Cardakli, E; Tran, N; Hassan-Zahraee, M; Ye, Z; Hyde, C; Hung, K; Chen, A; Ng, C; Grier, A; Lukin, D; Scherl, E; Targan, SR; Diehl, GE; Grootjans, J; Putoczki, TL; Wicks, I; Longman, RS;
- Journal Title
- Immunity
- Publication Type
- Jan 22
- 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.
- Publisher
- Cell Press
- Keywords
- Gm-csf; Ibd; Tl1a; colitis-associated cancer; emergency granulopoiesis; innate lymphoid cells; neutrophils
- Research Division(s)
- Inflammation; Personalised Oncology
- PubMed ID
- 41576959
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2025.12.008
- Open Access at Publisher's Site
https://doi.org/10.1016/j.immuni.2025.12.008- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-29 02:00:45
Last Modified: 2026-01-29 02:01:03