Added effects of dexamethasone and mesenchymal stem cells on early Natural Killer cell activation

Michelo, Clive M.; Fasse, Esther; Cranenbroek, Bram van; Linda, Katrin; Meer, Arnold van der; Abdelrazik, Heba; Joosten, Irma

doi:10.1016/j.trim.2016.04.008

Cited by 26 publications

(22 citation statements)

References 49 publications

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“…Inhaled corticosteroids (ICS) are potent immunomodulators and high doses of ICS are routinely administered in response to COPD exacerbations. Indeed, high doses of ICS use has been shown, both in vivo and in vitro, to be associated with alterations to NK surface phenotype and function 10,11 . Therefore, patients with an exacerbation and possible ICS use in the month prior to enrollment were excluded.…”

Section: Resultsmentioning

confidence: 99%

Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease

Osterburg

Lach

Panos

et al. 2020

Sci Rep

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open Scientific RepoRtS | (2020) 10:1238 | https://doi.org/10.1038/s41598-020-58326-7www.nature.com/scientificreports www.nature.com/scientificreports/ cytolytic response of NK cells. Activated cells release cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα), among others, which recruit and activate other immune system cells. Perforin release from NK cells causes pore formation in target cell membranes; proteases such as granzyme A and B can enter the cell to induce apoptosis by caspase cleavage as well as cleave other cellular targets. Therefore, aberrant and/or chronic activation of NK cells can result in chronic inflammation and tissue damage.Given the morbidities and economic burden of COPD and AECOPD, it is important to examine the immune function of these patients in greater detail than previous studies. In this study, we utilized polychromatic flow cytometry to measure the expression of an array of activating and inhibitory receptors on peripheral blood natural killer cells from never smokers, current smokers, and COPD patients. We identified >1,000 significant and unique NK cell subpopulations using the Scalable Weighted Iterative Flow-clustering Technique (SWIFT) 6-8 . These data reveal several changes in the expression of NK cell activating/inhibitory receptors and the size of the NK cell subpopulations associated with smoking and COPD. Furthermore, we demonstrate that logistic regression analysis using population size and receptor expression from peripheral blood NK cells is highly predictive of patients with a previous exacerbation. These findings provide an entry point to more closely examine the effects of smoking on NK cell phenotype and function, the role of NK cells in COPD exacerbations, and the use of NK cells as biomarkers for exacerbations. Scientific RepoRtS |(2020) 10:1238 | https://doi.

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Section: Resultsmentioning

confidence: 99%

Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease

Osterburg

Lach

Panos

et al. 2020

Sci Rep

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“…However, there is evidence that steroid treatment may have a beneficial effect on MSC function as well. Dexamethasone treated MSCs suppress IFN-γ, perforin, and CD69 expression in NK cell populations (48). In addition, we have previously shown that loading MSCs with intracellular microparticles containing budesonide enhances their suppression of peripheral blood mononuclear cells (PBMCs) (2).…”

Section: Discussionmentioning

confidence: 99%

Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Burand

Boland

et al. 2020

Front. Immunol.

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Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into "spheroids," which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been thoroughly determined. In this study, we discovered that aggregation of MSCs into spheroids causes them to lose their T cell-suppressive abilities. Interestingly, adding budesonide, a topical glucocorticoid steroid, alongside spheroids partially restored MSC suppression of T cell proliferation. Through a series of inhibition and add-back studies, we determined budesonide acts synergistically with spheroid MSC-produced PGE2 to suppress T cell proliferation through the PGE2 receptors EP2 and EP4. These findings highlight critical differences between adherent and spheroid MSC interactions with human immune cells that have significant translational consequences. In addition, we uncovered a mechanism through which spheroid MSC suppression of T cells can be partly restored. By understanding the phenotypic changes that occur upon MSC aggregation and the impact of MSC drug interactions, improved immunosuppressive MSC therapies for localized delivery can be designed.

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“…ELISA results revealed that HFC treatment significantly increased the secretion of PGE2 in BMSCs compared with that by untreated BMSCs, which was antagonized by NS-398, a specific inhibitor of COX-2, which is responsible for PGE2 production (Fig. 6A) (30). EP4 is the receptor for PGE2, an important transmembrane G protein-coupled receptor in macrophages (31).…”

Section: Expression Of Genes Associated With Inflammation In Raw2647mentioning

confidence: 98%

Modulation of the secretion of mesenchymal stem cell immunoregulatory factors by hydrolyzed fish collagen

Liu

Sun

2020

Exp Ther Med

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The aim of the present study was to investigate the possible immunomodulatory effects of osteogenically differentiated bone marrow mesenchymal stem cells induced by hydrolyzed fish collagen. Marine biomaterials have attracted significant attention for their environmental friendliness and renewability. Hydrolyzed fish collagen (HFC) has been discovered to induce the osteoblastic differentiation of stem cells, which underlies the foundation for its application in tissue engineering. Stem cells and their biomaterial carriers face acute immune rejection mediated by host macrophages. A potential strategy for combatting rejection in stem cell therapy is to modify the polarization of macrophages. However, whether HFC-induced mesenchymal stem cells maintain their immunomodulatory ability remains to be determined. To understand this phenomenon, a co-culture model of direct contact was established between bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages, where the secretion of nitrous oxide from macrophages was measured using Griess colorimetric assay. ELISAs were performed to measure the secretion of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and IL-10, whilst reverse transcription-quantitative PCR was used to assess the expression levels of IL-1β, IL-6, CD206, resistin-like molecule α (FIZZ1) and prostaglandin E2 receptor 4 (EP4). In addition, the expression levels of relevant proteins in the phosphorylated-cyclic AMP-responsive element-binding protein-CCAAT/enhancer-binding protein β (EBPβ) pathway were investigated using western blotting. HFC-induced BMSCs were found to suppress the expression levels of IL-1β and IL-6, whilst increasing the expression levels of CD206 and FIZZ1 in RAW264.7 macrophages. HFC-induced BMSCs also inhibited the secretion of IL-1β and IL-6, whilst promoting the secretion of TGF-β and IL-10 secretion from RAW264.7 macrophages. Mechanistic studies using western blotting discovered that HFC stimulated the secretion of prostaglandin E2 from BMSCs, which subsequently increased the expression of EP4 on the macrophages. EP4 then increased the expression levels of C/EBPβ and arginase 1 further. In conclusion, results from the present study suggested that following induction with HFC, BMSCs maintain their immunomodulatory activity.

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Added effects of dexamethasone and mesenchymal stem cells on early Natural Killer cell activation

Cited by 26 publications

References 49 publications

Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease

Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease

Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Modulation of the secretion of mesenchymal stem cell immunoregulatory factors by hydrolyzed fish collagen

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