Abstract

The lung offers one of the largest exchange surfaces of the individual with the elements of the environment. As a place of important interactions between self and non-self, the lung is richly endowed in various immune cells. As such, lung natural killer (NK) cells play major effector and immunoregulatory roles to ensure self-integrity. A better understanding of their abilities in health and diseases has been made possible over the past decade thanks to tremendous discoveries in humans and animals. By precisely distinguishing the different NK cell subsets and dissecting the ontogeny and differentiation of NK cells, both blood and tissue-resident NK populations now appear to be much more pleiotropic than previously thought. In light of these recent findings in healthy individuals, this review describes the different lung NK cell populations quantitatively, qualitatively, phenotypically, and functionally. Their identification, immunological diversity, and adaptive capacities are also addressed. For each of these elements, the impact of the mutual interactions of lung NK cells with environmental and microenvironmental factors are questioned in terms of functionality, competence, and adaptive capacities. As pulmonary diseases are major causes of morbidity and mortality worldwide, special attention is also given to the involvement of lung NK cells in various diseases, including infectious, inflammatory, autoimmune, and neoplastic lung diseases. In addition to providing a comprehensive overview of lung NK cell biology, this review also provides insight into the potential of NK cell immunotherapy and the development of targeted biologics.

Highlights

  • The lung is faced daily with 10,000 liter of inhaled air containing a myriad of particles, potentially recognized as non-self

  • The CD49a+ resident natural killer (NK) cells significantly express both CD69 and CD103 in much higher proportions than CD49a− NK cells. These different markers of lung residency are mostly expressed by the immature CD56brightCD16− and CD56dimCD16− NK cell subsets, whereas they are only slightly expressed by mature CD56dimCD16+ NK cells

  • NKG2C overexpression has not been demonstrated in lung NK cells from healthy donors [11], it could be hypothesized that, as being the site of many viral infections, the lung would be an interesting tissue in which to study the acquisition of NK cell memory [28]

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Summary

NK Cells in the Human Lungs

Edited by: Eric Vivier, INSERM U1104 Centre d’immunologie de Marseille-Luminy, France. By precisely distinguishing the different NK cell subsets and dissecting the ontogeny and differentiation of NK cells, both blood and tissue-resident NK populations appear to be much more pleiotropic than previously thought. In light of these recent findings in healthy individuals, this review describes the different lung NK cell populations quantitatively, qualitatively, phenotypically, and functionally. Their identification, immunological diversity, and adaptive capacities are addressed. In addition to providing a comprehensive overview of lung NK cell biology, this review provides insight into the potential of NK cell immunotherapy and the development of targeted biologics

INTRODUCTION
Identification of NK Cell Populations
Phenotypical and Functional Characterization of Lung NK Cells
LUNG NK CELLS IN DISEASES
Quantitative Modulation of Lung NK Cells
Presence of NK cells in BALF
Lung NK Cells in Inflammatory Diseases
Lung NK Cells in Infectious Diseases and Cancer
Findings
CONCLUSIONS AND PERSPECTIVES
Full Text
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