Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic
inflammation of the airway
#MMPMID33262481
Ng B
; Cook SA
; Schafer S
Exp Mol Med
2020[Dec]; 52
(12
): 1871-1878
PMID33262481
show ga
Interleukin (IL)-11 evolved as part of the innate immune response. In the human
lung, IL-11 upregulation has been associated with viral infections and a range of
fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming
growth factor-beta (TGF?) and other disease factors can initiate an autocrine
loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely
ERK-dependent manner, triggers the translation of profibrotic proteins. Lung
epithelial cells also express the IL-11 receptor and transition into a
mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic
targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced
pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade
of IL-11 signaling has anti-inflammatory effects, which suggests that lung
inflammation is sustained, in part, through IL-11 activity in the stroma.
Proinflammatory fibroblasts and their interaction with the damaged epithelium may
represent an important but overlooked driver of lung disease. Initially thought
of as a protective cytokine, IL-11 is now increasingly recognized as an important
determinant of lung fibrosis, inflammation, and epithelial dysfunction.
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