PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human Mesenchymal Stem Cells in Humanized Mice.

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Abstract

RATIONALE

Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSC) have been shown to be beneficial to pulmonary fibrosis as they have the immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSC in vivo.

METHODS

Here, to mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. Based on this model, the benefit of human MSC to pulmonary fibrosis and underlying mechanism were investigated. In addition, the relevant parameters in the patients with pulmonary fibrosis were also examined.

RESULTS

We demonstrated that human CD8+ T cells were critical for the induction of pulmonary fibrosis in humanized mice. Human MSC could alleviate pulmonary fibrosis and improve lung function by suppressing bleomycin-induced human T cell infiltration and pro-inflammatory cytokine productions in the lungs from humanized mice. Importantly, the alleviation of pulmonary fibrosis by human MSC was mediated by the PD-1/PD-L1 pathway. Moreover, the abnormal PD-1 expression was found in circulating T cells and lung tissues of the patients with pulmonary fibrosis.

CONCLUSION

Our study supports the potential benefit of targeting PD-1/PD-L1 pathway for the treatment of pulmonary fibrosis.

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