Natural Killer Cells in the Lungs

Cong, Jingjing; Wei, Haiming

doi:10.3389/fimmu.2019.01416

Cited by 97 publications

(106 citation statements)

References 157 publications

(168 reference statements)

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“…4A). We first analyzed the kinetics of innate NK cells subsets, that we defined as HLA-DR-CD3-cells expressing the NKG2a receptors, which are known to traffic to the lung 35 (Fig. 4B-D tSNE analysis revealed an increase in the level of PD-1 at weeks 2 and 3 post-infection, overlapping with spatial regions corresponding to both CD4+ T and CD8+ T cells (Fig.…”

Section: Nkg2a+ Cells and Pd-1+ T Cells Decrease In Blood And Increasmentioning

confidence: 99%

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Fahlberg

Blair

Doyle-Meyers

et al. 2020

Preprint

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We investigated the immune events following SARS-COV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a rapid migration of CD16+ monocytes from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial macrophages (HLA- DR+ CD206–), a transitional CD11c+ CD16+ population that was directly associated with IL-6 levels in plasma, and one long lasting CD11b+ CD16+ population. Strikingly, monocytes were a correlate of viral replication in bronchial brushes and levels of TARC (CCL17), and worse disease outcomes were associated with high levels of cell infiltration in lungs and CD11b+ CD16+ macrophages accumulation. Importantly, this accumulation was long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with less signs of disease had a high IL-10:IL-6 ratio. Our results unravel cellular mechanisms of COVID-19 and validate NHP as models to test immune therapies.

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Section: Nkg2a+ Cells and Pd-1+ T Cells Decrease In Blood And Increasmentioning

confidence: 99%

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Fahlberg

Blair

Doyle-Meyers

et al. 2020

Preprint

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“…There are several reports highlighting that properly stimulated γδ T cells can recognize and kill lung cancer cells, while they are altered in advanced NSCLC [101][102][103][104]. Along the same line, several studies have suggest that NK cells have a robust protective role against tumors in the early stages of lung cancer, but that they become dysfunctional in the late stages, allowing tumor evasion to occur [105,106]. Therefore, it is possible that the NK cell activation and γδ T cell expansion that are mediated by ROS1 electrovaccination may prolong their functionality and contribute to lung cancer impairment.…”

Section: Discussionmentioning

confidence: 99%

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

et al. 2020

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Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice.

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“…(ii) ILC plasticity has been demonstrated to be essential to shape ILC responses to diverse stimuli ( 113 , 114 , 140 ), which confers ILC subsets the capacities to change their phenotype and functions under specific circumstances, but nothing is known about the authentic metabolic alterations required for ILC plasticity. (iii) Recent findings show that functions of NK cells are markedly influenced by their local microenvironments, and that the unique characteristics of NK cells in different tissues have been uncovered step by step ( 141 , 142 ). Other ILCs are largely tissue-resident cells, and this tissue dwelling property and the specialized distribution of non-NK ILCs are coupled to their functional heterogeneity ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of Natural Killer Cells and Other Innate Lymphoid Cells

Cong

2020

Front. Immunol.

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Natural killer (NK) cells are the host's first line of defense against tumors and viral infections without prior sensitization. It is increasingly accepted that NK cells belong to the innate lymphoid cell (ILC) family. Other ILCs, comprising ILC1s, ILC2s, ILC3s and lymphoid tissue inducer (LTi) cells, are largely non-cytotoxic, tissue-resident cells, which function to protect local microenvironments against tissue insults and maintain homeostasis. Recently, evidence has accumulated that metabolism supports many aspects of the biology of NK cells and other ILCs, and that metabolic reprogramming regulates their development and function. Here, we outline the current understanding of ILC metabolism, and describe how metabolic processes are affected, and how metabolic defects are coupled to dysfunction of ILCs, in disease settings. Furthermore, we summarize the current and potential directions for immunotherapy involving targeting of ILC metabolism. Finally, we discuss the open questions in the rapidly expanding field of ILC metabolism.

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Natural Killer Cells in the Lungs

Cited by 97 publications

References 157 publications

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

Metabolism of Natural Killer Cells and Other Innate Lymphoid Cells

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