IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

ABSTRACT: Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway¹, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues², induces TLSs. In mice, Il33 deficiency severely attenuates inflammation- and LTβR-activation-induced TLSs in models of colitis and pancreatic ductal adenocarcinoma (PDAC). In PDAC, the alarmin domain of IL-33 activates group 2 innate lymphoid cells (ILC2s) expressing LT that engage putative LTβR⁺ myeloid organizer cells to initiate

SUBMITTER: Amisaki M 

PROVIDER: S-EPMC11864983 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature