Generation and Characterisation of Th22 Cells Identifies a Unique Molecular Profile

Interleukin-22 (IL-22) belongs to the IL-10 cytokine family and is expressed in many tissues during chronic inflammatory diseases, including asthma and rhinitis. IL-22 can have both pro-inflammatory and tissue protective roles, which depend on the inflammatory context, tissue tropisms, and local cytokine milieu. How IL-22 exerts its varying effects remains poorly understood. Recently, a novel lineage of CD4⁺ T helper cells (known as Th22 cells) have been identified that predominantly express IL-22, but not IL-17. Th22 cells have subsequently been associated with the pathogenesis of asthma, atopic dermatitis and psoriasis. The functional role of these Th22 cells in inflammatory responses remains largely unknown, due to an inability to characterise their function directly in vitro or in vivo. Knowledge of the factors controlling Th22 cell differentiation in vitro remains limited, making phenotypic and functional characterisation of these cells difficult. We have identified, for the first time, critical differentiation factors that promote the polarisation and outgrowth of large numbers of Th22 cells in vitro. Through fate mapping studies, we demonstrate that Th22 cells develop independently of the Th17 lineage. Further, using novel T cell transgenic reporter mice, we have specifically isolated purified Th22 cells using FACS. Phenotypic characterisation of the Th22 transcriptome identified a unique expression profile, distinct from Th17 cells. Our study provides valuable techniques for the assessment of Th22 function and its role in immunity. An improved understanding of Th22 function in mucosal tissues in asthma and rhinitis will provide insight into disease processes and potential novel targets for therapeutic intervention.