scholarly journals The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients

2022 ◽  
Vol 10 (A) ◽  
pp. 6-11
Author(s):  
Yan Wisnu Prajoko ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Adi Muradi Muhar ◽  
Nur Dina Amalina

BACKGROUND: Mesenchymal stem cells (MSCs) have potent immunosuppressive properties to control systemic lupus erythematosus (SLE) disease by releasing several anti-inflammatory molecules, particularly indoleamine 2, 3-dioxygenase (IDO), and increasing regulatory T cells (Treg) to control innate and adaptive immune cells. However, how MSCs release IDO to modulate Treg in controlling B is poorly understood. Therefore, investigating IDO, Treg, and B cells following MSC administration in SLE is needed. AIM: This study aimed to investigate the ameliorating effects of MSCs in controlling B cells mediated by an increase of IDO-induced Treg in PBMC of SLE patients. METHODS: This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups: Sham (placebo group), control, and three treatment groups. The treatment groups were treated by coculturing MSCs to PBMCs with a ratio of 1:10, 1:25, and 1:40 for 72 h incubation. Treg and B-cell levels were analyzed by flow cytometry with cytometric bead array (CBA) while the IDO levels were determined by ELISA. RESULTS: This study showed that the percentages of B cells decreased significantly in groups treated by dose-dependent MSCs, particularly in T1 and T2 groups followed by increased Treg cell percentages. These findings were aligned with the significant increase of the IDO levels. CONCLUSIONS: MSCs regulated B cells through an increase of IDO-induced Treg in SLE patients’ PBMC.

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sylvie Amu ◽  
Mikael Brisslert

Background. We have shown that approximately 30% of human peripheral blood B-cells express CD25. B cells expressing CD25 display a mature phenotype belonging to the memory B-cell population and have a better proliferative and antigen-presenting capacity. The aim of the present study was to characterize the CD25-expressing subset of B cells in human cord blood.Material and Methods. Mononuclear cell fraction from human cord blood (n=34) and peripheral adult blood (n=22) was sorted into CD20+CD25+and CD20+CD25-B-cell populations. Phenotype and function of these B-cell populations were compared using flow cytometry, proliferation, cytokine production, and immunoglobulin secretion.Results. CD25-expressing B cells are a limited population of cord blood mononuclear cells representing 5% of the CD20+B cells. They are characterised by high expression of CD5 in cord blood and CD27 in adult blood. CD25-expressing B cells express a functional IL-2 receptor and high levels of CC-chemokine receptors and spontaneously produce antibodies of IgG and IgM subclass.Conclusions. CD25 expression is a common denominator of a specific immunomodulatory B-cell subset ready to proliferate upon IL-2 stimulation, possibly ready to migrate and home into the peripheral tissue for further differentiation/action.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.


2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.


Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.


2019 ◽  
Vol 1 (2) ◽  
pp. 226-235
Author(s):  
Afnijar Wahyu ◽  
Liza Wati ◽  
Murad Fajri

The purpose of this study was to determine the effect of AIUEO therapy on the speech ability of stroke patients who have motor aphasia in Raja Ahmad Thabib Hospital Tanjungpinang. The research design used was quasi experiment with the Nonequivalent Control Group Design approach to 9 respondents who were divided into 9 treatment groups and 9 control groups. The results showed that there were significant differences in the functional ability of communication between the control and treatment groups with a value of p <0.05 (p = 0.007 at a = 0.05) using the Wilcoxon Test statistical test. Conclusion, the influence of AIUEO therapy on the speech ability of stroke patients with motor aphasia in the treatment and control groups at Ahmad Thabib Hospital Tanjungpinang.   Keywords: Speech Ability, Motor Aphasia Stroke, AIUEO Therapy


2019 ◽  
Vol 3 (1) ◽  
pp. 23-27
Author(s):  
Edy Soesanto ◽  
Edi Dharmana ◽  
Soeharyo Hadisaputro ◽  
Siti Fatimah Muis

Introduction: Bamboo shoot Gigantochloa apus extract has antioxidant compounds that act as lipid peroxidation inhibitors and reduce free radical formation so that it can be used as an anti-inflammatory and anti-oxidative stress in the atherosclerosis. Aim: Knowing the effect of bamboo shoot Gigantochloa apus extract in reducing MDA levels and IL-10 increasing levels in rabbits given atherogenic diet. Methods: This experiment used randomized pre-test and post-test with control group design, in 24 New Zealand White rabbits divided into 4 groups randomly. MDA and IL-10 levels were examined by the ELISA method. Results and conclusion: Bamboo shoot Gigantochloa apus extract can reduce MDA levels and increase IL-10 levels significantly in accordance with increasing doses. The increase of MDA levels in the control group with all treatment groups was different (p = 0.0001), and between the treatment groups and other treatment groups there were also differences (p


2018 ◽  
Vol 24 (1) ◽  
pp. 37
Author(s):  
Annisa Trissatharra ◽  
Sri Ratna Dwiningsih ◽  
Ratna Sofaria Munir

Objectives: To identify the effect of monoclonal antibody bZP3 at ovarian follicles that undergo atresia and diameter of various ovarian follicles.Materials and Methods: This is a true experimental research with post only control group design. Samples were 36 female mices (Mus musculus) which is divided into 6 groups, there are 3 control groups (group 1, 2, and 3) injected by Phospatase Buffer Saline (PBS) 50µl and 3 treatment groups (group 4, 5, and 6) injected by Mab bZP3 50µl. Group 1 and 4 terminated at 5th day, group 2 and 5 terminated at 10th day, and group 3 and 6 terminated at 20th day. Evaluation of atretic ovarian follicles and diameter of ovarian follicles performed by hematoxylin eosin (HE) and the data processed by parametric statistic.Results: There are no significant in different among groups in the aspect of atretic follicles and diameter of folicles (p>0.05), but descriptively, number of follicles undergo atresia of the follicle primary, secondary, and tertiary treatment group was higher than the control group, except on the 20th day of observation time.Conclusion: administration of Mab bZP3 had no effect to amount of atretic follicles and diameter of folicles during observation time.


2018 ◽  
Vol 54 (2) ◽  
pp. 84 ◽  
Author(s):  
Widayati Agustina ◽  
Widjiati Widjiati ◽  
Alfiah Hayati

This study aimed to determine the effects of red fruit (Pandanus conoideus Lam) oil on MDA levels and spermatozoa quality in mice (Mus musculus) exposed to MSG. The quality includes motility, viability, concentration, and morphology of spermatozoa. This experimental study used randomized post-test only control group design. The subjects of this study were 25 mice (Mus musculus), divided into 5 groups (5 mice per group). K- group received distilled water for 35 days. K+ group received 4 mg/g BW MSG for 21 days. P1, P2, and P3 treatment groups received 4 mg/g BW MSG for 21 days and 0.02; 0.04; 0.08 ml/g BW red fruit oil, respectively, from day 22 to 35. The results showed that mean spermatozoa morphology in K-, K+, P1, P2, P3 groups were as follows: 0.86; 0.56; 0.67; 0.61; and 0.87 (%). The spermatozoa concentrations were sequentially as follows: 21; 10; 15; 32,8,19 (107 cells/ml). The spermatozoa's vitalities were as follows: 0,64; 0,14; 0,24; P2: 0.36; 0.68 (%). MDA levels were respectively: 0.29; 0.60; 0.35; 0.23; and 0.19 (nm). As a conclusion, testicular MDA levels in mice exposed to MSG and given with red fruit oil were lower than those in mice exposed to MSG without receiving red fruit oil. The quality of spermatozoa in mice exposed to MSG and receiving red fruit oil was higher than that of mice exposed to MSG without being given with red fruit oil.


2020 ◽  
Vol 56 (3) ◽  
pp. 208
Author(s):  
Arista Wahyu Ningsih ◽  
Maftuchah Rochmanti ◽  
Achmad Basori

The survey results in Indonesia in 2017 showed that the diarrhea morbidity rate for all age groups was 6.897.463. In Indonesia, unripe wooden banana has been used empirically as an antidiarrheal by the people in Senduro village, Lumajang, East Java. The study aimed to prove the antidiarrheal effect of ethanol extract of unripe wooden banana (Musa paradisiaca L.) in male Balb-C/mice induced by Escherichia coli bacteria. This study was a laboratory experimental study with post-test only control group design that used 40 mice divided into 8 groups, namely 1 group without treatment (normal mice) and 7 groups induced by Escherichia coli (1 negative control group given CMC-Na, 3 groups positive controls were given Loperamid HCL 0,5 mg/kgBW, 1 mg/kgBW and 2 mg/kgBW and 3 treatment groups were given extracts 100 mg/kgBW, 200 mg/kgBW and 400 mg/kgBW). Observation of animals in this study was carried out for 4 hours. Data were analyzed of frequency of diarrhea, fecal weight and fecal consistency used Kruskal Wallis and the results showed significant differences between treatment groups (p <0.05). From the results of the Mann-Whitney test, the ethanol extract of unripe wooden banana with a dose of 100 mg/kgBW was not significantly different (p> 0.05) with the control group of Loperamid HCL dose of 0.5 mg/kgBW. Unripe wooden banana had been shown to have antidiarrheal activity at an extract dose of 100 mg/kg BW in terms of the parameters of fecal consistency, frequency of diarrhea, and fecal weight. The results showed that the higher the dose, the better antidiarrheal activity.


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