Clinical and Experimental Medicine

, Volume 19, Issue 4, pp 487–494 | Cite as

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

  • L BergantiniEmail author
  • P Cameli
  • M d’Alessandro
  • C Vagaggini
  • RM Refini
  • C Landi
  • MG Pieroni
  • M Spalletti
  • P Sestini
  • E Bargagli
Original Article


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.


Natural killer cells Natural killer T-like cells Bronchoalveolar lavage Interstitial lung diseases 



Lung function tests


Bronchoalveolar lavage


Natural killer cells


Natural killer T-like cells


Idiopathic pulmonary fibrosis


Non-specific interstitial pneumonia


Chronic fibrotic hypersensitivity pneumonitis


Interstitial lung diseases


Forced vital capacity


Forced expiratory volume in the first second


Diffuse lung carbon monoxide


Author 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.


The study was conducted at Siena University without funding sponsors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10238_2019_578_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Respiratory Disease and Lung Transplant Unit, Department of Medical Sciences, Surgery and NeurosciencesSiena UniversitySienaItaly
  2. 2.Department of Life SciencesSiena UniversitySienaItaly

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