Shining light on the significance of NK cell CD56 brightness

Poznanski, Sophie M.; Ashkar, Ali A.

doi:10.1038/s41423-018-0163-3

Cited by 32 publications

(28 citation statements)

References 12 publications

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“…Previous studies have shown that dNK cells contain lower level of PRF1 and GzmB than CD56 bright and CD56 dim peripheral NK cells (pNK). According to literature reports, it had demonstrated that dNK cells represent the limited cytotoxicity compared with peripheral blood NK cells, despite the fact that dNK cells express the perforin, granzyme A and granzyme B, and several NK‐activating receptors . CD56 bright CD16 − NK cells, predominant in decidual tissue, display poorly cytolytic activity and produced a variety of chemokines and cytokines, particularly IFN‐r and TNF‐α .…”

Section: Discussionmentioning

confidence: 99%

CD49a regulates the function of human decidual natural killer cells

Hou

Zhang

et al. 2019

American J Rep Immunol

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| INTRODUC TI ONAs a member of an integrin family, CD49a is expressed on a variety of immune cells including T cells, natural killer T cells (NKT), and NK cells. CD49a plays important roles in innate and adaptive immunemediated responses as well as in inflammation, regulation of growth, differentiation, 1 and liver cirrhosis. 2,3 CD8 + CD49a + Trm (Tissue-resident memory T cells) cells and CD8 + CD49a − Trm cells exert significantly different immune effects. 4 CD49a also regulates the migration, retention, and preservation of immune cells. Interaction of CD49a with collagen promotes immune cells proliferation and the secretion of inflammatory cytokines, which upregulate the expression of CD49a on endothelial cells and mesangial cells, promoting the formation of blood vessels. 2,3 In normal pregnancy, embryonic trophoblast cells and maternal decidual stromal cells comprise the maternal-fetal interface. NK cells, components of the innate immune system, are concentrated within the decidual tissue of the maternal-fetal interface. 5,6 A recent study has shown integrin, αvβ3, to regulate adhesion between villous trophoblastic cells. When a small molecule inhibitor (SB-273005) was used to inhibit the expression of Problem: The function of CD49a on human decidual natural killer (dNK) cells is unknown. Method of study: The expression of CD49a on dNK cells from human patients with recurrent spontaneous abortions or age-matched healthy controls was analyzed by flow cytometry. DNK cells were treated with CD49a neutralizing antibody and analyzed for function (cytokines production and cytotoxic activity). Long non-coding RNA (lncRNA) microarray analysis was used to identify a potential regulator of CD49a. Results: DNK cells from human patients who underwent recurrent spontaneous abortions had lower levels of CD49a and increased perforin, granzyme B, and IFN-r expression, when compared to dNK cells from age-matched healthy controls. Perforin, granzyme B, and IFN-r expression levels in dNK cells were upregulated, while the migration and adhesion of dNK cells were downregulated by CD49a-neutralizing antibody. By the 51 Cr release assay, the killing activity of dNK cells also increased with CD49a neutralizing antibody. Further, lnc-49a, a newly identified lncRNA, was shown to be a positive regulator of CD49a in primary human NK cells. Conclusion: CD49a is involved in the regulation of dNK cells functions, including cytotoxic activity, migration, and adhesion. Further, lnc-49a is a positive regulator of CD49a in human primary dNK cells. K E Y W O R D S adhesion, CD49a, long non-coding RNAs, migration, natural killer cells S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Li H, Hou Y, Zhang S, et al. CD49a regulates the function of human decidual natural killer cells. Am J Reprod Immunol. 2019;81:e13101. https://doi.

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Section: Discussionmentioning

confidence: 99%

CD49a regulates the function of human decidual natural killer cells

Hou

Zhang

et al. 2019

American J Rep Immunol

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“…This is also contrary to the conventional knowledge that mature and memory-like NKG2A − selfKIR + CD57 + NKG2C + NK cells generated by cytokine stimulation or CMV infection are more efficacious [93,94,95,96,97,98]. Although a unifying explanation for these seemingly contradictory findings is not yet available, recent observations suggest that the phenotype of NK cells determines the function, and CD56 bright or CD56 superbright NK cells may not only differentiate into mature cytotoxic NK cells, but also secrete enough cytokines to overcome the immunosuppressive tumor microenvironment [99]. Furthermore, those cytokines may induce the differentiation of cancer stem cells limiting their ability to expand and metastasize [100].…”

Section: Strategies To Enhance the Effect Of Nk Cell Therapymentioning

confidence: 99%

“…Furthermore, those cytokines may induce the differentiation of cancer stem cells limiting their ability to expand and metastasize [100]. Thus, the limitations of autologous NK cell therapy may be overcome by converting patient NK cells into a CD56 bright or CD56 superbright phenotype, rather than CD56 dim [62,99]. In addition, the conventional designation of maturity by the degree of CD56 fluorescence should be reconsidered.…”

Section: Strategies To Enhance the Effect Of Nk Cell Therapymentioning

confidence: 99%

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

Lee

Kwack

et al. 2019

Cancers

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In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. In this regard, the autologous NK cell therapy is safer. This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. A recent study discovered that NK cell specific genetic defects are closely associated with the tumor immune microenvironment that determines clinical outcomes. This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors.

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“…CD56 has an unclear function itself and its “brightness” is not a good discriminator when it comes to implications of surface expression on NK cell functions. CD56 bright NK cells are considered to be non-cytotoxic and with immunoregulatory functions, but they can also exhibit enhanced cytotoxicity and degranulation against viral and tumor antigens (35). Along these lines, even absence of CD56 on NK cells marks a specific subset of CD56 neg NK cells resembling CD56 dim with moderate responsiveness and differential expression of several granule proteins (36, 37).…”

Section: Discussionmentioning

confidence: 99%

29-Color Flow Cytometry: Unraveling Human Liver NK Cell Repertoire Diversity

et al. 2019

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Recent studies have demonstrated extraordinary diversity in peripheral blood human natural killer (NK) cells and have suggested environmental control of receptor expression patterns on distinct subsets of NK cells. However, tissue localization may influence NK cell differentiation to an even higher extent and less is known about the receptor repertoire of human tissue-resident NK cells. Advances in single-cell technologies have allowed higher resolution studies of these cells. Here, the power of high-dimensional flow cytometry was harnessed to unravel the complexity of NK cell repertoire diversity in liver since recent studies had indicated high heterogeneity within liver NK cells. A 29-color flow cytometry panel allowing simultaneous measurement of surface tissue-residency markers, activating and inhibitory receptors, differentiation markers, chemokine receptors, and transcription factors was established. This panel was applied to lymphocytes across three tissues (liver, peripheral blood, and tonsil) with different distribution of distinct NK cell subsets. Dimensionality reduction of this data ordered events according to their lineage, rather than tissue of origin. Notably, narrowing the scope of the analysis to the NK cell lineage in liver and peripheral blood separated subsets according to tissue, enabling phenotypic characterization of NK cell subpopulations in individual tissues. Such dimensionality reduction, coupled with a clustering algorithm, identified CD49e as the preferred marker for future studies of liver-resident NK cell subsets. We present a robust approach for diversity profiling of tissue-resident NK cells that can be applied in various homeostatic and pathological conditions such as reproduction, infection, and cancer.

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Shining light on the significance of NK cell CD56 brightness

Cited by 32 publications

References 12 publications

CD49a regulates the function of human decidual natural killer cells

CD49a regulates the function of human decidual natural killer cells

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

29-Color Flow Cytometry: Unraveling Human Liver NK Cell Repertoire Diversity

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