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Fernandez, I.E. ; Greiffo, F.R. ; Frankenberger, M. ; Bandres, J. ; Heinzelmann, K. ; Neurohr, C.* ; Hatz, R.* ; Hartl, D.* ; Behr, J.* ; Eickelberg, O.

Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis.

Eur. Respir. J. 48, 1171-1183 (2016)
Publ. Version/Full Text Supplement Supplement DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disease with irreversible lung function loss and poor survival. Myeloid-derived suppressor cells (MDSC) are associated with poor prognosis in cancer, facilitating immune evasion. The abundance and function of MDSC in IPF is currently unknown.Fluorescence-activated cell sorting was performed in 170 patients (IPF: n=69; non-IPF interstitial lung disease (ILD): n=56; chronic obstructive pulmonary disease (COPD): n=23; healthy controls: n=22) to quantify blood MDSC and lymphocyte subtypes. MDSC abundance was correlated with lung function, MDSC localisation was performed by immunofluorescence. Peripheral blood mononuclear cell (PBMC) mRNA levels were analysed by qRT-PCR.We detected increased MDSC in IPF and non-IPF ILD compared with controls (30.99±15.61% versus 18.96±8.17%, p≤0.01). Circulating MDSC inversely correlated with maximum vital capacity (r= -0.48, p≤0.0001) in IPF, but not in COPD or non-IPF ILD. MDSC suppressed autologous T-cells. The mRNA levels of co-stimulatory T-cell signals were significantly downregulated in IPF PBMC. Importantly, CD33(+)CD11b(+) cells, suggestive of MDSC, were detected in fibrotic niches of IPF lungs.We identified increased MDSC in IPF and non-IPF ILD, suggesting that elevated MDSC may cause a blunted immune response. MDSC inversely correlate with lung function only in IPF, identifying them as potent biomarkers for disease progression. Controlling expansion and accumulation of MDSC, or blocking their T-cell suppression, represents a promising therapy in IPF.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Regulatory T-cells; Lung-cancer; Immune-response; Tumor Microenvironment; Fibrocytes; Differentiation; Infection; Tuberculosis; Dysfunction; Metastasis
ISSN (print) / ISBN 0903-1936
e-ISSN 1399-3003
Journal European Respiratory Journal
Quellenangaben Volume: 48, Issue: 4, Pages: 1171-1183 Article Number: , Supplement: ,
Publisher European Respiratory Society
Publishing Place Sheffield
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)