Il11-flox Mouse

Interleukin 11 (IL11) is a cytokine belonging to the IL6 family. Initially thought to be a haematopoietic and cytoprotective factor, recent data suggest it is redundant for haematopoiesis and can be toxic. IL11 signals via pathways like JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine after tissue injury, activating mesenchymal transition of epithelial, stromal, and endothelial cells, leading to inflammation, fibrosis, and stalled endogenous tissue repair [3].

In acute kidney injury, Il11 deletion or neutralizing IL11 antibody treatment in mice prevents SNAI1 expression and kidney dysfunction, highlighting IL11-induced mesenchymal transition of injured renal tubular epithelial cells as an important renal pathology [2]. In a mouse model of bleomycin-induced pulmonary fibrosis, inhaled siRNA nanoparticles targeting IL11 hinder fibroblast differentiation, reduce ECM deposition, and improve pulmonary function [1]. In a model of chronic kidney disease, anti-IL11 therapy promotes renal tubular epithelial cell proliferation, reverses fibroinflammation, and restores renal function [2]. In mice, genetic deletion of Il11 extends lifespan, and anti-IL11 treatment from 75 weeks of age improves metabolism, muscle function, and reduces ageing biomarkers and frailty [4].

In conclusion, IL11 plays a significant role in promoting inflammation, fibrosis, and mesenchymal transition in various tissues and organs, contributing to the pathogenesis of diseases such as pulmonary fibrosis, kidney diseases, and ageing-related pathologies. Gene knockout mouse models have been crucial in revealing these roles, highlighting IL11 as a potential therapeutic target for these diseases.