NK Cells in the Human Lungs

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.

Prostate cancer peripheral blood NK cells show enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 production, and secrete monocyte-recruiting and polarizing factors

“…In other tumours where pTA-NKs have been investigated, CD9 is present on the cell surface of a subset of circulating CD56 bright CD16 -/low ; dNK-like cells are present in pNK of melanoma [62][63][64], lung [12,28,65] and colorectal cancers [25,66].Based on our evidence we confirmed that, even when it is difficult to detect tumour infiltrating NK, peripheral blood NK cells offer and indirect tool monitor the state of cancer patients according to their polarization.…”

Harnessing Memory NK Cell to Protect Against COVID-19

“…Recently, Marquardt et al have identified a new adaptive-like KIR+/NKG2C+ NK cell subset with a CD49a+/CD56bright/CD16−trNK cell phenotype in human lung and in peripheral blood of HCMV-seropositive individuals, mentioned above (Marquardt et al, 2019). The adaptive-like lung trNK cells have been thus found to be hyper-responsive towards target cells (Hervier et al, 2019). This novel subset of human lung NK cells contributes to unique defense mechanisms in the context of the respiratory infection at this site (Cong and Wei, 2019).…”

Airway Natural Killer Cells and Bacteria in Health and Disease

“…Lung NK cells have recently been extensively reviewed in this journal (23,24), so that a summary of their most important features might be sufficient. Lungs are constantly exposed to microparticles from the environment.…”

“…Particularly, as the mucosal lung epithelium is at the interface between the outside world and the organism, it can become the entry site for infectious pathogens, be they bacterial, fungal, or viral in nature. Therefore, an extensive and sophisticated local immune response is waiting to be triggered at this anatomic location, and human NK cells, which represent around 5-20% of lung lymphocytes (24), are a part of it. The work of Marquardt et al has established that most human lung NK cells represented the circulating subset and had the mature CD56 dim CD16 bright phenotype (25).…”