scholarly journals Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner

2017 ◽  
Vol 14 (11) ◽  
pp. 895-908 ◽  
Author(s):  
Kyung-Ah Cho ◽  
Jun-Kyu Lee ◽  
Yu-Hee Kim ◽  
Minhwa Park ◽  
So-Youn Woo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Dependent Manner ◽  
Regulatory B Cells

scholarly journals SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zhe Chen ◽  
Shufen Zhou ◽  
Jianyun Li ◽  
Hui Li ◽  
Can Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Immune Thrombocytopenia ◽  
Mononuclear Cells ◽  
Dependent Manner ◽  
B Cell Differentiation ◽  
Regulatory B Cell

B cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induce immunosuppression, and stromal cell-derived factor-1α (SDF-1α) plays an important role in the migration and survival of MSCs. To investigate the mechanism of SDF-1α in controlling umbilical cord-derived MSCs (UC-MSCs) in inducing regulatory B cell differentiation of patients with ITP, we reconfirmed that SDF-1α promotes the proliferation of MSCs at the low doses of 0.05 μg/mL and 0.1 μg/mL but inhibits the proliferation and promotes the apoptosis of UC-MSCs at the high doses 0.5 μg/mL and 1 μg/mL; when UC-MSCs are cocultured with SDF-1α at 0.1 μg/mL, the decreased proportion of CD19+/CD24hi/CD38hi cells and IL-10-producing B cells (B 10 cell), considered as the Breg subset from ITP significantly enhanced, and the content of IL-10 in the supernatant is also obviously increased. The proportion of Bregs and the IL-10 secretion could be further promoted by the UC-MSCs treated with 0.1 μg/mL SDF-1α, which could also promote the miRNA-133 expression of UC-MSCs in an exosome-dependent manner; moreover, while the UC-MSCs were transfected with the miR-133 inhibitor, the proportion of induced Bregs decreased obviously when cocultured with peripheral blood mononuclear cells (PBMCs) of ITP. We conclude that UC-MSCs could effectively enhance the decreased proportion of Bregs from ITP; at appropriate concentrations, SDF-1α may promote the proliferating and survival ability of UC-MSCs and improve the production of Bregs induced by UC-MSCs through controlling miRNA-133 expression in the exosomes.

scholarly journals Effect of Human Mesenchymal Stem Cells on Xenogeneic T and B Cells Isolated from Lupus-Prone MRL.Faslpr Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hong Kyung Lee ◽  
Eun Young Kim ◽  
Hyung Sook Kim ◽  
Eun Jae Park ◽  
Hye Jin Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dependent Manner ◽  
T And B Cells

Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by hyperactivation of T and B cells. Human mesenchymal stem cells (hMSCs) ameliorate the progression of SLE in preclinical studies using lupus-prone MRL.Faslpr mice. However, whether hMSCs inhibit the functions of xenogeneic mouse T and B cells is not clear. To address this issue, we examined the in vitro effects of hMSCs on T and B cells isolated from MRL.Faslpr mice. Naïve hMSCs inhibited the functions of T cells but not B cells. hMSCs preconditioned with IFN-γ (i) inhibited the proliferation of and IgM production by B cells, (ii) attracted B cells for cell–cell interactions in a CXCL10-dependent manner, and (iii) inhibited B cells by producing indoleamine 2,3-dioxygenase. In summary, our data demonstrate that hMSCs exert therapeutic activity in mice in three steps: first, naïve hMSCs inhibit the functions of T cells, hMSCs are then activated by IFN-γ, and finally, they inhibit B cells.

Human mesenchymal stem cells modulate B-cell functions

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 367-372 ◽  
Author(s):  
Anna Corcione ◽  
Federica Benvenuto ◽  
Elisa Ferretti ◽  
Debora Giunti ◽  
Valentina Cappiello ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Costimulatory Molecule ◽  
Human Mesenchymal Stem Cells ◽  
B Cell Differentiation ◽  
Major Mechanism ◽  
Cell Functions

Abstract Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.

scholarly journals Human Adipose Tissue-Derived Mesenchymal Stem Cells Abrogate Plasmablast Formation and Induce Regulatory B Cells Independently of T Helper Cells

Stem Cells ◽  
2015 ◽  
Vol 33 (3) ◽  
pp. 880-891 ◽  
Author(s):  
M. Franquesa ◽  
F. K. Mensah ◽  
R. Huizinga ◽  
T. Strini ◽  
L. Boon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
B Cells ◽  
T Helper Cells ◽  
Human Adipose Tissue ◽  
Regulatory B Cells ◽  
T Helper ◽  
Helper Cells

Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1519-1529 ◽  
Author(s):  
Peter Reichardt ◽  
Bastian Dornbach ◽  
Song Rong ◽  
Stefan Beissert ◽  
Faikah Gueler ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Dependent Manner ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Immunologic Synapse

Abstract Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell–dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell–primed regulatory T cells, “bTregs,” as a useful approach for therapeutic intervention in adverse adaptive immune responses.

Effect of Mesenchymal Stem Cells on the Viability, Proliferation and Differentiation of B Lymphocytes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3880-3880
Author(s):  
Soraya Tabera ◽  
Jose A. Perez-Simon ◽  
Maria Diez-Campelo ◽  
Luis I. Sanchez-Abarca ◽  
Belen Blanco ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Annexin V ◽  
B Cell Differentiation ◽  
Cells Cultured

Abstract Mesenchymal stem cells (MSC) are multilineage non hematopoietic progenitor cells that play a key role in supporting the lymphohematopoietic system. Their distribution in bone marrow and secondary lymphoid organs allows an intimate interaction with T and B-lymphocytes, which contribute to the normal lymph node development, but this interaction, can not be considered as a simple bi-directional cross-talk and other cell subsets, such as dendritic cells (DC), must be considered. We have analysed the effect of MSC on B-lymphocytes and the pathways involved in these effects. For these propose, we cultured B-cell with or without MSC and analysed different markers involved in the differentiation of B-cells. We found that MSC inhibited proliferation, arresting B lymphocytes in G0G1 phase of cell cycle (figure 1). However, the presence of MSC increased the viability ob B-lymphocytes (double number of viable B-cells: from 13012 to 22835 Annexin-V PE/7 ADD negative events within B-lymphocytes in absence versus presence of MSC). The exposure of B-cells to plasmocytoid DC (pDC) induced B-lymphocytes differentiation increasing both the percentage of CD38++/CD138++ cells as well as the mean fluorescence intensity of both markers (figure 2). Accordingly, different B-cell subpopulations could be identified which represented a continuum in B-cell maturation. While the levels of cytoplasmic immunoglobulin (cIg) were higher among CD38++ cells, the opposite occurred for the expression of surface Ig as well as CD19 and CCR7. Interestingly, the presence of MSC blocked B-cell differentiation. Regarding the pathways involved in these effects, the presence of MSC influenced on ERK 1/2 and p38 pathways, but these effects depended on the culture conditions. Thus, MSC induced phosphorilation of ERK 1/2 MAPK and inhibited phosphorilation of p38 in B-cells cultured with Ig plus CpG (low proliferative conditions) while the contrary occurred in B-cells cultured with TPA (highly proliferative conditions). Therefore we demonstrated that MSC increased viability and blocked cell cycle of B-lymphocytes. Furthermore the plasmocitoid dendritic cells favoured B-lymphocytes differentiation and this process in inhibited in presence with MSC. These effects are at least in part mediated through the ERK 1/2 and p38 pahtways. Figure Figure

scholarly journals Tafazzin deficiency in mouse mesenchymal stem cells potentiates their immunosuppression and impairs activated B lymphocyte immune function

2021 ◽  
Author(s):  
Hana M. Zegallai ◽  
Ejlal Abu-El-Rub ◽  
Folayemi Olayinka-Adefemi ◽  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Genetic Disorder ◽  
Interleukin 10 ◽  
Barth Syndrome ◽  
Wild Type ◽  
The Impact

AbstractBarth Syndrome (BTHS) is a rare X-linked genetic disorder caused by mutation in the TAFAZZIN gene which encodes the cardiolipin (CL) transacylase tafazzin (Taz). Taz deficiency in BTHS patients results in reduced CL in their tissues and a neutropenia which contributes to the risk of infections. However, the impact of Taz deficiency in other cells of the immune system is poorly understood. Mesenchymal stem cells (MSCs) are well known for their immune inhibitory function. We examined whether Taz-deficiency in murine MSCs impacted their ability to modulate lipopolysaccharide (LPS)-activated wild type (WT) murine B lymphocytes. MSCs from tafazzin knockdown (TazKD) mice exhibited a 50% reduction in CL compared to wild type (WT) MSCs. However, mitochondrial oxygen consumption rate and membrane potential were unaltered. In contrast, TazKD MSCs exhibited increased glycolysis compared to WT MSCs and this was associated with elevated proliferation, phosphatidylinositol-3-kinase expression and expression of the immunosuppressive markers indoleamine-2,3-dioxygenase, cytotoxic T-lymphocyte-associated protein 4, interleukin-10, and cluster of differentiation 59. When co-cultured with LPS-activated WT B cells, TazKD MSCs inhibited B cell proliferation and growth rate and reduced B cell secretion of IgM to a greater extent than B cells co-cultured with WT MSCs. In addition, co-culture of LPS-activated WT B cells with TazKD MSCs induced B cell differentiation toward potent immunosuppressive phenotypes including interleukin-10 secreting plasma cells and B regulatory cells compared to activated B cells co-cultured with WT MSCs. These results indicate that Taz deficiency in MSCs enhances MSCs-mediated immunosuppression of activated B lymphocytes.

scholarly journals Impact of Placenta-Derived Mesenchymal Stem Cells Treatment on Patients with Severe Lung Injury Caused by COVID-19 Pneumonia: Clinical and Immunological Aspect

2021 ◽  
Author(s):  
Mei-Chuan Chen ◽  
Kevin Shu-Leung Lai ◽  
Ko-Ling Chien ◽  
Sing-Teck Teng ◽  
Yuh-Rong Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Lung Injury ◽  
Immune Responses ◽  
Critically Ill ◽  
Treg Cells ◽  
Control Group ◽  
Current Standard

Abstract Background:The novel coronavirus disease 2019 (COVID-19) has been a global pandemic health issue since 30, January, 2020. Mortality rate was as high as more than 50% in critically ill patients. The Stem cell treatment is effective in refractory severe critically ill COVID-19 patients, but immune regulation mechanisms have not been reported well. Therefore, we evaluate the clinical efficacy and immune modulation of placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) in severe critically ill COVID-19 infection who are refractory to current standard therapies.Methods:Intravenous infusion of 1 × 107 MatriPlax was given to five severe COVID-19 patients at Day 0 and day 4. Serum inflammatory markers and immune profiles were studied at Day 0, 4 and 8. Clinical parameters and 28-days mortality were compared between treated group and control group.Results:The treatment group had no 28-days mortality and Murray’s lung injury score was significantly improved compared with control group. After treatment, Ferritin, C-reactive protein (CRP) and Lactate dehydrogenases (LDH) were significantly reduced and lymphopenia was improved. IL-6, IL-1β, IFN-γ and IL-2 were significantly decreased together with decrease in IL-10 reflecting decreasing intensity of inflammation. Immune cell profiles showed increase in CD4+ T cells (CD4+ naïve T cells, CD4+ memory T cells subtypes), Treg cells, CD19+ B cells (and CD19+ naive B cells, CD27+ switched B cells subtypes) and dendritic cells, and a significant decrease in CD14+ monocytes (and CD16- classical, CD16+ non-classical subtypes) monocytes as well as plasma/plasmablast cells. pc-MSCs treatment suppressed hyper-inflammatory states of innate immune responses to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoted CD4+ T cells and CD19+ B cells towards adaptive immune responses.Conclusion:The intravenous transplantation of Matriplax was safe and effective for severe critically ill COVID-19 patients, especially those who were refractory to current standard care and immunosuppressive therapies

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