ORIGINAL ARTICLE Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis Thomas P. Hofer & Marion Frankenberger & Irene Heimbeck & Dorothe Burggraf & Matthias Wjst & Adam K. A. Wright & Maria Kerscher & Susanne Nährig & Rudolf M. Huber & Rainald Fischer & Loems Ziegler- Heitbrock Received: 27 March 2014 /Revised: 15 July 2014 /Accepted: 29 July 2014 # Springer-Verlag Berlin Heidelberg 2014 Abstract We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cy- tometry) and mRNA level (RT-PCR) in adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del ho- mozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ group1 ) and 36 below (average 1.24 ΔMnI, CF-DQ group2 ). Also, the CD16- positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF- DQ group2 patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQ group2 . MHC class II transcripts were reduced in CF with a sevenfold de- crease in HLA-DQβ1 for CF-DQ group2 patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysac- charide reduced HLA-DQ expression. Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA- DQ expression in CF, which is associated with inflam- mation and a reduced response to IFNγ. Key message • CF patients show a reduced expression of MHCII mole- cules in monocytes and macrophages. • HLA-DQ and HLA-DR transcript levels are also reduced in CF patients. • CF patient C-reactive protein levels correlate with low HLA-DQ expression. • Reduced expression of MHC class II molecules appears to be linked to inflammation. • CF patients exhibit an impaired response to IFNgamma. Keywords Cystic fibrosis . HLA-DQ . HLA-DR . Inflammation . Monocytes, macrophages and dendritic cells T. P. Hofer (*) : M. Frankenberger : I. Heimbeck : D. Burggraf : L. Ziegler- Heitbrock Comprehensive Pneumology Center and EvA Study Center, Helmholtz Zentrum München, German Research Center for Environmental Health and Asklepios Fachkliniken München-Gauting, Koch-Allee 29, 82131 Gauting, Germany e-mail: hofer@helmholtz-muenchen.de M. Wjst Institute for Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany A. K. A. Wright : L. Ziegler- Heitbrock Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK M. Kerscher : S. Nährig : R. M. Huber : R. Fischer Medizinische Klinik Innenstadt, Abteilung Pneumologie, Klinikum der Ludwig-Maximilians Universität, München, Germany Present Address: A. K. A. Wright Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, UK Present Address: R. Fischer Medical Practice, Munich-Pasing, Germany J Mol Med DOI 10.1007/s00109-014-1200-z