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NK and NKT-like cells in granulomatous and fibrotic lung diseases

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Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and granulomatous of unknown etiology are unclear. Objectives Here we investigated NK and NKT-like cells in peripheral blood (PB) and Bronchoalveolar lavage (BAL) from patients with ILDs. Method 190 patients (94 male mean age 61 ± 14.3 years) and 8 controls undergoing bronchoscopy for ILD diagnostic work-up were enrolled consecutively; 115 patients sarcoidosis, 24 chronic fibrotic hypersensitivity pneumonitis and 43 patients other ILDs [32 idiopathic pulmonary fibrosis (IPF) and 11 non-specific interstitial pneumonia (NSIP)]. PB and BAL were processed by flow cytometry using monoclonal antibodies to differentiate NK and NKT-like cells. Results NK% in BAL was significantly different among ILDs (p = 0.02). Lower NK% was observed in BAL from sarcoidosis than other ILDs (p < 0.05). Similar findings were observed for NKT-like, whereas no differences were found for PB NK%. Difference of NK% was observed between BAL and PB in all groups (p < 0.001). Sarcoidosis patients reported the best area under the curve for NKT-like (AUC = 0.678, p = 0.0015) and NK cells (AUC = 0.61, p = 0.001). In the IPF-NSIP subgroup, NK% cell was inversely correlated with FVC% (r = − 0.34, p = 0.03) and DLCO% (r = − 0.47, p = 0.0044). Conclusions NK and NKT-like were expressed differently in BAL from patients with different ILD and were significantly depleted in sarcoidosis respect to other ILDs. This suggests that these cells may play a protective role in the pathogenesis of sarcoidosis.

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Abbreviations

LFT:

Lung function tests

BAL:

Bronchoalveolar lavage

NK:

Natural killer cells

NKT-like:

Natural killer T-like cells

IPF:

Idiopathic pulmonary fibrosis

NSIP:

Non-specific interstitial pneumonia

cHP:

Chronic fibrotic hypersensitivity pneumonitis

ILD:

Interstitial lung diseases

FVC:

Forced vital capacity

FEV1:

Forced expiratory volume in the first second

DLco:

Diffuse lung carbon monoxide

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Funding

The study was conducted at Siena University without funding sponsors.

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Authors and Affiliations

  1. Respiratory Disease and Lung Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, Siena, Italy

    L Bergantini, P Cameli, M d’Alessandro, C Vagaggini, RM Refini, MG Pieroni, M Spalletti, P Sestini & E Bargagli

  2. Department of Life Sciences, Siena University, Siena, Italy

    C Landi

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  1. L Bergantini
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Contributions

LB conducted the study. LB and PC helped to define the study objectives and to coordinate the study. LB, PC and Md performed the statistical analysis and interpreted the results, CL, RMR and MP collected the data, MS and CV performed experiment, LB, EB and PS wrote the first draft of the manuscript. All authors critically revised the manuscript and approved its final version.

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Correspondence to L Bergantini.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Local Ethics Committee C.E. A. V. S. E. (Code Number 180712) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Bergantini, L., Cameli, P., d’Alessandro, M. et al. NK and NKT-like cells in granulomatous and fibrotic lung diseases. Clin Exp Med 19, 487–494 (2019). https://doi.org/10.1007/s10238-019-00578-3

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