Flip‐flops of natural killer cells in autoimmune diseases versus cancers: Immunologic axis

Shahrabi, Saeid; Zayeri, Zeinab Deris; Ansari, Nazli; Hadad, Elham Homaei; Rajaei, Elham

doi:10.1002/jcp.28421

Cited by 8 publications

(5 citation statements)

References 132 publications

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“…It has been reported that lymphocytes such as monocyte cells and NK cells could express TNF-α upon activation, exhibiting tumor cytotoxicity effects. , Therefore, we then analyzed whether higher levels of TNF-α could be detected in the supernatant of incubated lymphocytes. According to the results, 72 h post treatment, the concentration of TNF-α in the supernatant of the CLPP/mIL-15 group increased to more than 3-fold than that of the control group, as detected by the ELISA assay (Figure G).…”

Section: Resultsmentioning

confidence: 99%

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation

et al. 2020

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Immunogene therapy is a novel method for the treatment of colorectal cancer. Cytokine IL-15 has exhibited therapeutic anticancer potential due to its immune-stimulation property. However, conventional IL-15-based cancer gene therapy studies have been performed using the plasmid DNA form, which has potential shortcomings including weak delivery efficiency and backbone effect. In this study, an IL-15 immunogene therapy study for colon cancer using in vitro transcript mRNA is described. A protamine/liposome system (CLPP) is developed to provide efficient condensation and delivery capacity for in vivo mRNA transportation. They demonstrated that the prepared CLPP system could deliver the IL-15-encoding mRNA into C26 cells with high efficacy. The secretory expressed IL-15 cytokine by the C26 cells successfully produced lymphocyte stimulation and triggered anticancer cytotoxicity upon cancer cells in vitro. Local or systemic administration of the CLPP/mIL-15 complex exhibited obvious inhibition effects on multiple C26 murine colon cancer models with inhibition rates of up to 70% in the C26 abdominal cavity metastasis tumor model, 55% in the subcutaneous model, and 69% in the pulmonary metastasis model, demonstrating high efficacy and safety. These results successfully demonstrated the high therapeutic potential of the CLPP/mIL-15 complex for colorectal cancer immunogene therapy.

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Section: Resultsmentioning

confidence: 99%

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation

et al. 2020

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“…NK cells are potent immune effectors already known to be important for controlling the outcomes of pregnancy, infection and cancer. Distinct NK cell subsets drive inflammation or impact immunoregulatory functions, and restrict adaptive immune responses that may otherwise lead to autoimmunity [49][50][51]. Variation in NK cell function within and between individuals is known to correspond with diversity in health outcomes, making this population highly interesting for study and precise immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO

2020

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Natural killer (NK) cells are innate lymphocytes with functions that include target cell killing, inflammation and regulation. NK cells integrate incoming activating and inhibitory signals through an array of germline-encoded receptors to gauge the health of neighbouring cells. The reactive potential of NK cells is influenced by microRNA (miRNA), small non-coding sequences that interfere with mRNA expression. miRNAs are highly conserved between species, and a single miRNA can have hundreds to thousands of targets and influence entire cellular programs. Two miRNA species, miR-155-5p and miR-146a-5p are known to be important in controlling NK cell function, but research to best understand the impacts of miRNA species within NK cells has been bottlenecked by a lack of techniques for altering miRNA concentrations efficiently and without off-target effects. Here, we describe a nonviral and straightforward approach for increasing or decreasing expression of miRNA in primary human NK cells. We achieve >90% transfection efficiency without off-target impacts on NK cell viability, education, phenotype or function. This opens the opportunity to study and manipulate NK cell miRNA profiles and their impacts on NK cellular programs which may influence outcomes of cancer, inflammation and autoimmunity.

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“…sNKG2DL can also affect the recognition of pathogens by NK cells, reduce the cytotoxicity of NK cells, and inhibit the immune surveillance function of NK cells [40]. However, in autoimmune diseases, NK cells may enhance the immune response due to the production of cytokines that regulate the immune response [41]. A study by Schepis et al in nephritis, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) patients and healthy individuals showed that NK cells stimulated antibody production and exacerbated the disease in patients with SLE [42].…”

Section: Nkg2d-lmentioning

confidence: 99%

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

Wei,

Xiang,

Zou

2023

IJMS

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Natural killer (NK) cells and CD8+ T cells can clear infected and transformed cells and generate tolerance to themselves, which also prevents autoimmune diseases. Natural killer group 2 member D (NKG2D) is an important activating immune receptor that is expressed on NK cells, CD8+ T cells, γδ T cells, and a very small percentage of CD4+ T cells. In contrast, the NKG2D ligand (NKG2D-L) is generally not expressed on normal cells but is overexpressed under stress. Thus, the inappropriate expression of NKG2D-L leads to the activation of self-reactive effector cells, which can trigger or exacerbate autoimmunity. In this review, we discuss the role of NKG2D and NKG2D-L in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type I diabetes (T1DM), inflammatory bowel disease (IBD), and celiac disease (CeD). The data suggest that NKG2D and NKG2D-L play a pathogenic role in some autoimmune diseases. Therefore, the development of strategies to block the interaction of NKG2D and NKG2D-L may have therapeutic effects in some autoimmune diseases.

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Flip‐flops of natural killer cells in autoimmune diseases versus cancers: Immunologic axis

Cited by 8 publications

References 132 publications

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation

Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation

Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

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