Genomic expression profiling of NK cells in health and disease

Wang, Fuyan; Tian, Zhigang; Wei, Haiming

doi:10.1002/eji.201444998

Cited by 13 publications

(13 citation statements)

References 92 publications

(206 reference statements)

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“…3c; Supplementary Table 1). In contrast, transcripts mainly confined to mNK cells2425262728, such as the integrins CD49b ( Itga2 ) and CD11b ( Itgam ), Cx3cr1 , S1pr5 and several members of the Ly49 receptor family ( Klra1 , Klra3 , Klra9 and Klra7 ), were present albeit downregulated in eNK cells (Fig. 3c; Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis

et al. 2016

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Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122+CD49b+ cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM). We confirm the NK-cell identity of these cells by transcriptome-wide analyses and their ability to eliminate tumour cells. Rather than using the conventional pathway of NK-cell development, IL-12-driven CD122+CD49b+ cells remain confined to a NK1.1lowNKp46low stage, but differentiate into NK1.1+NKp46+ cells in the presence of γc-cytokines. Our data reveal an IL-12-driven hard-wired pathway of emergency NK-cell lymphopoiesis bypassing steady-state γc-signalling.

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Section: Resultsmentioning

confidence: 99%

Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis

et al. 2016

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“…However, the mechanisms leading to an increased susceptibility to infections after stroke are still poorly understood. As an important component of innate immunity, NK-cell activation plays key roles in early host defense against pathogens by killing infected cells and/or producing cytokines (e.g., IFN-g, TNF-a) (46)(47)(48). Following this clue, we investigated whether NK-cell activation contributes to the host's defense against poststroke infections.…”

Section: Discussionmentioning

confidence: 99%

Activation of JAK/STAT3 restores NK‐cell function and improves immune defense after brain ischemia

et al. 2018

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Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ. Because the phenotype and function of peripheral NK cells have been widely investigated in ischemic stroke, nCounter Inflammation Gene Array Analysis was used to build immune-related gene profiles of NK cells to comprehensively analyze the molecular signature of NK cells after ischemic brain injury. We observed distinct gene expression profiles reflecting different splenic NK-cell phenotypes and functional properties across the time course of transient middle cerebral artery occlusion (MCAO). Based on gene expression and pathway-network analysis, lower expression levels of signal transducer and activator of transcription-3 (STAT3) were observed in animals with MCAO compared with sham control animals. Genetic activation of STAT3 through the introduction of STAT3 clustered regularly interspaced short palindromic repeats (CRISPR) plasmid prevented the loss of NK-cell-derived IFN-γ production after MCAO, together with reduced bacterial burden and mortality. Our data suggest that brain ischemia impairs NK-cell-mediated immune defense in the periphery, at least in part through the JAK-STAT3 pathway, which can be readdressed by modulating STAT3 activation status.-Jin, W.-N., Ducruet, A. F., Liu, Q., Shi, S. X.-Y., Waters, M., Zou, M., Sheth, K. N., Gonzales, R., Shi, F.-D. Activation of JAK/STAT3 restores NK-cell function and improves immune defense after brain ischemia.

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“…CD56 dim CD16 C NK cells display a higher cytotoxic activity, whereas CD56 bright CD16 ¡/low NK cells are more efficient in cytokine production. 92 Flow cytometry analysis on tissue samples and peripheral blood from PTC and MNG patients showed that tumor-infiltrating NK cells were increased in PTCs compared to goiters and healthy thyroids, whereas no differences were found in peripheral blood NK cells. In PTC patients, NK cell infiltration negatively correlated with disease stage.…”

Section: Nk: Natural Killer Cellsmentioning

confidence: 98%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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Genomic expression profiling of NK cells in health and disease

Cited by 13 publications

References 92 publications

Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis

Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis

Activation of JAK/STAT3 restores NK‐cell function and improves immune defense after brain ischemia

The immune network in thyroid cancer

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