Protective function of interleukin-22 in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor-beta (TGF-beta) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin-22 (IL-22) in the pathogenesis of IPF by regulating the TGF-beta pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL-22R knock out (IL-22RA1(-/-)) and IL-22 supplementation mouse models were used to determine if IL-22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL-22 and/or TGF-beta 1. In a clinical cohort, the expression level of IL-22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL-22 expression was associated with poorer pulmonary function. IL-22R(-/-) mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL-22 augmentation by intranasal instillation of recombinant IL-22 repressed inflammation and fibrotic phenotype. In vitro, IL-22 treatment repressed TGF-beta 1 induced gene markers representing epithelial-mesenchymal-transition and fibroblast-myofibroblast-transition, likely via the inhibition of TGF-beta receptor expression and subsequent Smad2/3 activation. IL-22 appears to be protective against pulmonary fibrosis by inhibiting TGF-beta 1 signaling, and IL-22 augmentation may be a promising approach to treat IPF.

Automated summary

IPF is a chronic lung disease with unknown cause, and the role of IL-22 in inhibiting TGF-beta 1 signaling pathway could be protective against pulmonary fibrosis. IL-22 shows potential as a therapeutic target for treating IPF.