IL-17 links the tumor suppressor LKB1 to gastrointestinal inflammation and polyposis.

ABSTRACT: Mutations in the tumor suppressor liver kinase B1 (LKB1) promote the development of gastrointestinal (GI) polyps of unknown etiology. Here, we identify IL-17 as a novel driver of LKB1-dependent polyp growth. GI tumors from mice bearing heterozygous mutations in Stk11 (which encodes LKB1) display signatures of pathogenic IL-17-producing CD4⁺ T helper 17 (T_H17) cells. LKB1 constrains T cell inflammatory potential, as Stk11/LKB1 haploinsufficiency promotes T cell differentiation toward pathogenic IL-17-producing T cell lineages (CD4⁺ T_H17 and CD8⁺ T_c17) in vitro and following intestinal infection. Mechanistically, aberrant CREB-regulated transcription coactivator 2 (CRTC2)-dependent signaling drives pathogenic T

SUBMITTER: Compton SE 

PROVIDER: S-EPMC12180503 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature