title: Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis.
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.
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors: Isis E
authors: IE
authors: Fernandez
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors: Flavia R
authors: FR
authors: Greiffo
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors: Marion
authors: M
authors: Frankenberger
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors: Julia
authors: J
authors: Bandres
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors: Katharina
authors: K
authors: Heinzelmann
authors: Asklepios Fachkliniken München-Gauting, Munich, Germany Comprehensive Pneumology Center, Medizinische Klinik und Poliklinik V, Klinikum der Ludwig-Maximilians-Universität, Member of the German Center of Lung Research (DZL), Munich, Germany.
authors: Claus
authors: C
authors: Neurohr
authors: Asklepios Fachkliniken München-Gauting, Munich, Germany.
authors: Rudolf
authors: R
authors: Hatz
authors: Children's Hospital of the University of Tübingen, Pediatric Infectiology, Immunology and Cystic Fibrosis, Tübingen, Germany Roche Pharma Research and Early Development (pRED), Immunology, Inflammation and Infectious Diseases (I3) Discovery and Translational Area, Basel, Switzerland.
authors: Dominik
authors: D
authors: Hartl
authors: Asklepios Fachkliniken München-Gauting, Munich, Germany Comprehensive Pneumology Center, Medizinische Klinik und Poliklinik V, Klinikum der Ludwig-Maximilians-Universität, Member of the German Center of Lung Research (DZL), Munich, Germany.
authors: Jürgen
authors: J
authors: Behr
authors: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany oliver.eickelberg@helmholtz-muenchen.de.
authors: Oliver
authors: O
authors: Eickelberg
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002469:Cell Separation; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology* / Q000503:physiopathology; D007107:Immune System; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000097:blood; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology*; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger