BACKGROUND: Natural killer cells (NK) and innate lymphoid cells with their subsets (ILC) are part of the innate immune system. OBJECTIVE: The aim is to evaluate how NK cells and ILC cells interact in atopic dermatitis (AD) patients (with and without dupilumab therapy) compared to control group. MATERIALS AND METHODS: Complete dermatological examination was performed in all patients included in the study (19 AD patients with dupilumab, 17 AD patients without dupilumab). Surface molecules expressed on NK cells and ILC cells were analyzed by flow cytometry. The association between NK cells and total ILC cells, ILC-1, ILC-2, ILC-3, NCR+ILC3, NCR-ILC3 were compared in AD patients and in the control group. The non-parametric Spearman's rank correlation coefficient was used for this statistical analysis. We evaluated the association of parameters with AD severity at the time of treatment.Non-parametric Mann-Whitney, Kolmogorov-Smirnov tests were used. RESULTS: We confirmed the higher association between NK cells and total ILC cells in AD patients without dupilumab therapy (in 30.3 %) and in healthy controls (in 27.2 %); this association is low in AD patients with dupilumab therapy (in 0.1 %). The higher association was confirmed between NK cells and ILCs subsets only in AD patients without dupilumab therapy; in these patients the highest association was confirmed between NK cells and ILC-2 cells (in 38.6 %). No statistically significant difference in the count of NK cells and ILC cells was found between mild and moderate form of AD patients treated with dupilumab. CONCLUSION: Targeting these cell types or the cytokines they produce could represent potential therapeutic strategies for controlling inflammation and alleviating symptoms in AD patients.
- MeSH
- atopická dermatitida * farmakoterapie imunologie MeSH
- buňky NK * imunologie účinky léků MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty imunologie účinky léků MeSH
- mezibuněčná komunikace MeSH
- mladý dospělý MeSH
- podskupiny lymfocytů imunologie účinky léků MeSH
- přirozená imunita účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: RTX toxin action often defines the outcome of bacterial infections. Here, we discuss the progress in understanding the impacts of RTX toxin activities on host immunity. RECENT FINDINGS: Bordetella pertussis CyaA activity paralyzes sentinel phagocytic cells by elevating cellular cAMP levels and blocks differentiation of infiltrating monocytes into bactericidal macrophages, promoting also de-differentiation of resident alveolar macrophages into monocyte-like cells. Vibrio cholerae multifunctional autoprocessing repeats-in-toxins (MARTX), through Rho inactivating and α/β-hydrolase (ABH) domain action blocks mitogen-activated protein kinase signaling in epithelial cells and dampens the inflammatory responses of intestinal epithelia by blocking immune cell recruitment. The action of actin crosslinking effector domain and Ras/Rap1-specific endopeptidase (RRSP) domains of MARTX compromises the phagocytic ability of macrophages. Aggregatibacter actinomycetemcomitans LtxA action triggers neutrophil elastase release into periodontal tissue, compromising the epithelial barrier and promoting bacterial spreads into deeper tissue. SUMMARY: Action of RTX toxins enables bacterial pathogens to cope with the fierce host immune defenses. RTX toxins often block phagocytosis and bactericidal reactive oxygen species and NO production. Some RTX toxins can reprogram the macrophages to less bactericidal cell types. Autophagy is hijacked for example by the activity of the V. cholerae ABH effector domain of the MARTX protein. Subversion of immune functions by RTX toxins thus promotes bacterial survival and proliferation in the host.
- MeSH
- adaptivní imunita MeSH
- Bacteria metabolismus patogenita MeSH
- bakteriální toxiny toxicita MeSH
- buňky NK účinky léků MeSH
- dendritické buňky účinky léků MeSH
- epitelové buňky účinky léků MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- monocyty účinky léků MeSH
- virulence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In our study, we focused on possible effects of supplementation with glucan and vitamin D on total numbers of NK cells in patients with diabetic retinopathy. We evaluated possible relations among nutritional state (BMI), leptin levels, and total numbers of NK cells in patients supplemented with (1) glucan and vitamin D, (2) vitamin D and placebo, and (3) vitamin D alone. Our results show that 3 months of supplementation with both glucan and vitamin D resulted in significant improvements of NK cell numbers. In addition, we found statistically significant correlation between NK cell numbers and leptin levels. Based on these results, we propose that the molecule responsible for these changes is glucan, as vitamin D alone or together with placebo caused no effects.
- MeSH
- beta-glukany aplikace a dávkování farmakologie MeSH
- buňky NK cytologie účinky léků MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- diabetická retinopatie farmakoterapie MeSH
- imunomodulace MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet lymfocytů MeSH
- potravní doplňky * MeSH
- senioři MeSH
- vitamin D aplikace a dávkování krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The increasing risk of acute large-scale exposure of ionising irradiation on the population underlines the necessity of developing effective radioprotective and mitigating agents. The aim of this work was to investigate the effect of sodium orthovanadate pre-treatment on mice exposed to high doses of gamma rays (from 5 to 13 Gy). The determination of median lethal dose within 30 days confirmed that orthovanadate applied to total-body-irradiated mice intra-peritoneally has a radioprotective but not a mitigating effect. With orthovanadate pre-treatment, the composition of cellularity in the bone marrow improved substantially and the main lymphocyte populations restored during the first month after irradiation. These findings contribute to 'gap-filling' in radioprotective effects and demonstrate the importance of haematological parameters in radiation-response prediction.
- MeSH
- B-lymfocyty účinky léků MeSH
- buňky NK účinky léků MeSH
- celotělové ozáření * MeSH
- inhibitor p21 cyklin-dependentní kinasy metabolismus MeSH
- ionizující záření MeSH
- kostní dřeň účinky léků účinky záření MeSH
- lymfocyty účinky léků účinky záření MeSH
- makrofágy metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- průtoková cytometrie MeSH
- radioprotektivní látky farmakologie MeSH
- T-lymfocyty účinky léků MeSH
- vanadáty farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Relapsed acute myeloid leukemia (AML) is a significant post-transplant complication lacking standard treatment and associated with a poor prognosis. Cellular therapy, which is already widely used as a treatment for several hematological malignancies, could be a potential treatment alternative. Natural killer (NK) cells play an important role in relapse control but can be inhibited by the leukemia cells highly positive for HLA class I. In order to restore NK cell activity after their ex vivo activation, NK cells can be combined with conditioning target cells. In this study, we tested NK cell activity against KG1a (AML cell line) with and without two types of pretreatment-Ara-C treatment that induced NKG2D ligands (increased activating signal) and/or blocking of HLA-KIR (killer-immunoglobulin-like receptors) interaction (decreased inhibitory signal). Both treatments improved NK cell killing activity. Compared with target cell killing of NK cells alone (38%), co-culture with Ara-C treated KG1a target cells increased the killing to 80%. Anti-HLA blocking antibody treatment increased the proportion of dead KG1a cells to 53%. Interestingly, the use of the combination treatment improved the killing potential to led to the death of 85% of KG1a cells. The combination of Ara-C and ex vivo activation of NK cells has the potential to be a feasible approach to treat relapsed AML after hematopoietic stem cell transplantation.
- MeSH
- akutní myeloidní leukemie imunologie terapie MeSH
- buňky NK účinky léků imunologie transplantace MeSH
- cytarabin farmakologie MeSH
- imunosupresiva farmakologie MeSH
- imunoterapie metody MeSH
- klinické zkoušky jako téma MeSH
- kultivované buňky MeSH
- lektinové receptory NK-buněk - podrodina K imunologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- receptory KIR imunologie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Význam tumor infiltrujících lymfocytů (tumor-infiltrating lymphocytes, TIL) a jejich vztah k prognóze nemocných byl rozsáhle studován u celé řady malignit. Výsledky metaanalýz poukazují především na pozitivní vliv lymfocytární infiltrace na celkovou dobu přežití a též na možnost predikce odpovědi na léčbu imunoterapií u pacientů se stanovenou denzitou lymfocytárního infiltrátu v nádoru. Nejde však jen o zastoupení buněk, ale i o jejich funkční vlastnosti vyjádřené expresí povrchových i intracelulárních znaků. Potenciál TIL je zřejmý. Podaří-li se vytvoření jednotných guidelines pro měření a interpretaci TIL v nádoru, získáme účinný nástroj pro rozhodování v rámci terapeutického algoritmu.
The role of the tumor-infiltrating lymphocytes (TIL) and its relationship to prognosis has been extensively studied in multiple cancers. Systematic reviews and meta-analysis have shown a positive correlation between the lymphocyte infiltration and the overall survival (OS) and also have revealed the possibility of predicting therapeutic response to immunotherapy by evaluating the lymphocyte density in the tumor. However, the presence of tumor infiltrating lymphocytes must be described together with the functional features and the phenotypic patterns of the cells. The potential of TIL is evident and therefore, establishing systematic guidelines for evaluation and interpretation of TIL may provide a powerful tool in predicting the survival of the patient and selecting an optimal therapeutic approach.
- MeSH
- buňky NK klasifikace účinky léků MeSH
- CD8-pozitivní T-lymfocyty * klasifikace účinky léků MeSH
- imunoterapie metody trendy MeSH
- kolorektální nádory klasifikace prevence a kontrola MeSH
- lidé MeSH
- melanom klasifikace prevence a kontrola MeSH
- metaanalýza jako téma MeSH
- nádory jater klasifikace prevence a kontrola MeSH
- nádory prsu klasifikace prevence a kontrola MeSH
- nádory vaječníků klasifikace prevence a kontrola MeSH
- nádory žaludku klasifikace prevence a kontrola MeSH
- prognóza * MeSH
- tumor infiltrující lymfocyty * klasifikace účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antigeny CD20 účinky léků MeSH
- autoimunitní nemoci MeSH
- B-lymfocyty imunologie MeSH
- buňky NK imunologie účinky léků MeSH
- encefalitida imunologie MeSH
- modely nemocí na zvířatech MeSH
- monoklonální protilátky terapeutické užití MeSH
- roztroušená skleróza * imunologie patofyziologie patologie MeSH
- T-lymfocyty - podskupiny imunologie patologie MeSH
- Publikační typ
- novinové články MeSH
The current study explored the in vitro anticancer properties of Mesua ferrea stem bark (SB) extract towards human colon carcinoma HCT116 cells. SB was successively extracted with different solvents using soxhlet apparatus. MTT assay was employed to test toxicity against different cancer and normal cell lines. Active extract (n-Hexane) was fractionated by column chromatography (CC) to get the most active fraction (F-3). Series of in vitro assays were employed to characterize cytotoxic nature of F-3. Antioxidant properties of F-3 were assessed using DPPH, ABTS and FRAP assays followed by GC–MS analysis. Intracellular ROS levels were measured by DCFH-DA fluorescent assay. Finally, cell signalling pathways and their downstream proteins targeted by F-3 were studied using 10-cancer pathway and human apoptosis protein profilers and in silico docking studies. n-Hexane extract and its fraction (F-3) showed potent anti-proliferative effect against HCT 116. Programmed cell death (PCD) studies showed that F-3 modulated the expression of multiple proteins in HCT 116. F-3 showed weak antioxidant activity in all the models, while significant increase in ROS was observed in HCT 116. GC–MS analysis revealed that F-3 was majorly comprised of terpenes. Data of pathway profiler and in silico studies revealed that F-3 down-regulated the expression of NF-κB and HIF-1α pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.
- MeSH
- adaptorové proteiny signální transdukční MeSH
- apoptóza účinky léků MeSH
- buněčná smrt účinky léků MeSH
- buňky NK účinky léků ultrastruktura MeSH
- kolorektální nádory farmakoterapie genetika patologie MeSH
- Malpighiaceae chemie MeSH
- nádorové buněčné linie účinky léků MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- techniky in vitro MeSH
- terpeny farmakologie terapeutické užití MeSH
- Publikační typ
- práce podpořená grantem MeSH
Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment with low-dose interleukins themselves or in combination with hsp70 derived (TKD) peptide.
- MeSH
- B-lymfocyty účinky léků metabolismus MeSH
- buňky NK účinky léků metabolismus MeSH
- dospělí MeSH
- interleukin-15 farmakologie MeSH
- interleukin-2 farmakologie MeSH
- kohortové studie MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- peptidové fragmenty chemie farmakologie MeSH
- proteiny tepelného šoku HSP70 chemie metabolismus MeSH
- receptory imunologické metabolismus MeSH
- T-lymfocyty účinky léků metabolismus MeSH
- techniky in vitro MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
