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Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis

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Abstract

We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) 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 homozygous 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-DQgroup1) and 36 below (average 1.24 ΔMnI, CF-DQgroup2). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQgroup2 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-DQgroup2. MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQgroup2 patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide 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 inflammation and a reduced response to IFNγ.

Key message

• CF patients show a reduced expression of MHCII molecules 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.

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Acknowledgments

We thank Karl Staples, Clinical & Experimental Sciences, University of Southampton, UK, for his valuable support on cDNA microarray analysis. Furthermore, we thank Kerstin Skokann for excellent technical assistance.

Disclosure

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Author notes

  1. Adam K. A. Wright

    Present address: Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, UK

  2. Rainald Fischer

    Present address: Medical Practice, Munich-Pasing, Germany

Authors and Affiliations

  1. 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

    Thomas P. Hofer, Marion Frankenberger, Irene Heimbeck, Dorothe Burggraf & Loems Ziegler- Heitbrock

  2. Institute for Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Matthias Wjst

  3. Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK

    Adam K. A. Wright & Loems Ziegler- Heitbrock

  4. Medizinische Klinik Innenstadt, Abteilung Pneumologie, Klinikum der Ludwig-Maximilians Universität, München, Germany

    Maria Kerscher, Susanne Nährig, Rudolf M. Huber & Rainald Fischer

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  1. Thomas P. Hofer
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Correspondence to Thomas P. Hofer.

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Hofer, T.P., Frankenberger, M., Heimbeck, I. et al. Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis. J Mol Med 92, 1293–1304 (2014). https://doi.org/10.1007/s00109-014-1200-z

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  • DOI: https://doi.org/10.1007/s00109-014-1200-z

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