Review Highlights Interleukin-11's Broad Immunomodulatory Roles Beyond Fibrosis, Influencing Innate and Adaptive Cell Plasticity

Traditionally, Interleukin-11 (IL-11), a member of the IL-6 cytokine family, has been primarily recognized for its potent role in driving fibrosis and stromal remodeling, particularly in conditions like systemic sclerosis (SSc) and interstitial lung disease (ILD). Current therapeutic approaches for fibrotic diseases often target TGF-β, but a significant gap remains in fully understanding and addressing the complex interplay between fibrosis and immune dysregulation. Emerging evidence suggests that IL-11's influence extends far beyond extracellular matrix deposition, playing a sophisticated role in directly shaping immune cell behavior and plasticity, which this review aims to consolidate.

This comprehensive review systematically synthesizes current literature to delineate the multifaceted roles of IL-11 in immune cell plasticity, moving beyond its established pro-fibrotic functions. The authors examined evidence across various studies, focusing on how IL-11 influences phenotypic shifts within both innate and adaptive immune compartments. The review also explored the direct and indirect mechanisms of IL-11's effects on target cells and highlighted the therapeutic potential of modulating the IL-11 signaling axis using diverse modalities, including monoclonal antibodies, siRNAs, peptides, recombinant proteins, and small molecules.