Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 25:10:1416.
doi: 10.3389/fimmu.2019.01416. eCollection 2019.

Natural Killer Cells in the Lungs

Jingjing Cong  1   2   3 , Haiming Wei  1   2
Affiliations
Review

Natural Killer Cells in the Lungs

Jingjing Cong et al. Front Immunol. .

Abstract

The lungs, a special site that is frequently challenged by tumors, pathogens and other environmental insults, are populated by large numbers of innate immune cells. Among these, natural killer (NK) cells are gaining increasing attention. Recent studies have revealed that NK cells are heterogeneous populations consisting of distinct subpopulations with diverse characteristics, some of which are determined by their local tissue microenvironment. Most current information about NK cells comes from studies of NK cells from the peripheral blood of humans and NK cells from the spleen and bone marrow of mice. However, the functions and phenotypes of lung NK cells differ from those of NK cells in other tissues. Here, we provide an overview of human and mouse lung NK cells in the context of homeostasis, pathogenic infections, asthma, chronic obstructive pulmonary disease (COPD) and lung cancer, mainly focusing on their phenotype, function, frequency, and their potential role in pathogenesis or immune defense. A comprehensive understanding of the biology of NK cells in the lungs will aid the development of NK cell-based immunotherapies for the treatment of lung diseases.

Keywords: homeostasis; infection; inflammation; lung; lung cancer; natural killer cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Lung NK cells in homeostasis. NK cells account for 10–20% of lymphocytes in the human and mouse lungs, and these cells are located in the lung parenchyma. (A) NK cells in the lungs have a more mature phenotype compared to those in other tissues. In mice, lung NK cells express high levels of the mature markers NKp46, CD49b, CD11b, and Ly49s. In humans, lung NK cells are mostly composed of the CD56dimCD16+ subset, and highly differentiated CD57+NKG2A− NK cells are present at a higher frequency in the lungs than in matched peripheral blood. (B) The vast majority of lung NK cells are circulating, and the existence of a small percentage of seemingly tissue-resident NK cells in the lungs remains to be confirmed. (C,D) Lung NK cells are hypofunctional in homeostasis, and their cytotoxicity and IFN-γ production levels are lower than those of NK cells in the spleen and peripheral blood. IFN, interferon; NK, natural killer; PB, peripheral blood.
Figure 2
Figure 2
NK cell dysfunction in lung cancer. NK cells in the lung cancer microenvironment display attenuated cytotoxicity, impaired viability and a distinct phenotype, with downregulated expression of NKG2D, DNAM1, CD16, CD27, NKp30, NKp44, and NKp80 and upregulated expression of NKG2A, KIR2DL1, and KIR2DL2. Two mechanisms are involved in NK cell dysfunction in the lung cancer microenvironment. First, aberrant FBP1 expression in NK cells leads to dysfunction by inhibiting their viability and glycolysis. Second, increased microRNA-183 reduces DPA12 expression in NK cells and thus suppresses NK cells. The initiation of both mechanisms may be associated with tumor microenvironment-derived TGF-β. TGF-β, transforming growth factor-β; FBP1, fructose-1,6-bisphosphatase; IFN, interferon; NK, natural killer; DAP12, DNAX activating protein of12 kDa; TGFβR, transforming growth factor β receptor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Marquardt N, Kekalainen E, Chen P, Kvedaraite E, Wilson JN, Ivarsson MA, et al. . Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69−CD56dim cells. J Allergy Clin Immunol. (2017) 139:1321–30.e1324. 10.1016/j.jaci.2016.07.043 - DOI - PubMed
    1. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. (2008) 9:503–10. 10.1038/ni1582 - DOI - PubMed
    1. Stein-Streilein J, Guffee J. In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection. J Immunol. (1986) 136:1435–41. - PubMed
    1. Nogusa S, Ritz BW, Kassim SH, Jennings SR, Gardner EM. Characterization of age-related changes in natural killer cells during primary influenza infection in mice. Mech Ageing Dev. (2008) 129:223–30. 10.1016/j.mad.2008.01.003 - DOI - PubMed
    1. Abdul-Careem MF, Mian MF, Yue G, Gillgrass A, Chenoweth MJ, Barra NG, et al. . Critical role of natural killer cells in lung immunopathology during influenza infection in mice. J Infect Dis. (2012) 206:167–77. 10.1093/infdis/jis340 - DOI - PubMed

Publication types