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

Fernandez, Isis E.; Greiffo, Flavia R.; Frankenberger, Marion; Bandres, Julia; Heinzelmann, Katharina; Neurohr, Claus; Hatz, Rudolf; Hartl, Dominik; Behr, Jürgen und Eickelberg, Oliver (2016): Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis. In: European Respiratory Journal, Bd. 48, Nr. 4: S. 1171-1183

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0903-1936
• Sprache: Englisch