| Autor: |
Yuejuan Zheng, Jan Rehwinkel, Karl Blirando, Nasullah K Alham, Victoria St Noble, Emily Fraser, Emmanouela Repapi, Neil Ashley, Joseph M D Rastrick, Agne Antanaviciute, Colin Clelland, Rachel E. Rigby, Stephen S. Taylor, Rachel K. Hoyles, Ling-Pei Ho, Chaitanya Vuppusetty, Clare S. Hardman, Laura Denney, Valentina Iotchkova, Rachel Benamore |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.1101/2020.01.16.908749 |
| Popis: |
Idiopathic pulmonary fibrosis (IPF) is the most severe form of lung fibrosis. It is progressive, and has an extremely poor outcome and limited treatment options. The disease exclusively affects the lungs, and thus less attention has been focused on blood-borne immune cells. which could be a more effective therapeutic target than lung-based cells. Here, we questioned if circulating monocytes, which has been shown to be increased in IPF, bore abnormalities that might contribute to its pathogenesis. We found that levels of circulating monocytes correlated directly with the extent of fibrosis in the lungs, and increased further during acute clinical deterioration. Monocytes in IPF were phenotypically distinct, displaying increased expression of CD64, a type 1 IFN gene expression signature and a greater magnitude of type 1 IFN response when stimulated. These abnormalities were accompanied by markedly raised CSF-1 levels in the serum, prolonged survival of monocytesex vivo, and increased numbers of monocytes in lung tissue. Our study defines the key monocytic abnormalities in IPF, proposing type 1 IFN-primed monocytes as a potential driver of an aberrant repair response and fibrosis. It provides a rationale for targeting monocytes and identifies monocytic CD64 as a potential specific therapeutic target for IPF. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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