Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features.

ABSTRACT: Natural Killer (NK) cells play pivotal immunological roles including direct cytotoxic effector function and secretion of inflammatory and immunomodulating cytokines. In the context of chronic inflammation, NK cell fitness decreases during disease progression through currently unknown mechanisms. Here, we demonstrate that Interleukin-35 (IL-35) inhibits human NK cell proliferation, pro-inflammatory, and cytotoxic functions, while promoting secretion of TGF-β and proangiogenic factors in vitro. We show prolonged exposure to IL-35 converts both conventional and adaptive NK cells into CD9⁺CD103⁺CD49a⁺ ILC1-like cells via autocrine TGF-β. We assess cancer patient-derived public datasets and reveal the presence of IL-35-producing cells and IL-35-receptor-expressi

SUBMITTER: Picant V 

PROVIDER: S-EPMC12229632 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature