Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

Hoseinzadeh, Amin; Rezaieyazdi, Zahra; Mahmoudi, Mahmoud; Afshari, Jalil Tavakol; Arab, Fahimeh Lavi; Esmaeili, Seyed‐Alireza; Faridzadeh, Arezoo; Rezaeian, Amin; Hoseini, Sara; Barati, Mehdi; Mahmoudi, Alireza; Tabasi, Nafiseh

doi:10.1016/j.intimp.2023.109699

Cited by 4 publications

(16 citation statements)

References 170 publications

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“…All experiments were conducted using MSCs in passages 3–5. MSCs are characterized by adherence to plastic, expression of the surface molecules CD73, CD90, and CD105 without CD34, CD45, and CD11b surface molecules, and ability to differentiate into adipocytes and osteocytes mice, as previously shown [ 5 ].…”

Section: Methodsmentioning

confidence: 87%

“…Mouse primary MSCs were initially isolated from bone aspirates of 6- to 8-wk-old BALB/c, cultured, and identified precisely as previously reported [ 5 ]. In brief, femurs and tibias were isolated, cleaned from any remaining flesh, and flushed with culture media (low glucose Dulbecco’s modified Eagle’s medium (DMEM) with 1% penicillin/streptomycin and 15% fetal bovine serum, two mM L-glutamine) to extract the bone aspirates.…”

Section: Methodsmentioning

confidence: 99%

“…Accumulating data shows that MSCs are present in almost all tissues [ 3 ]. MSCs are a unique type of cells in a rest state (naïve MSCs) that track the “cues” from the inflamed and injured niches, migrate by adhering and spreading on the walls of blood vessels and tissues, sensing activation signals from pro-inflammatory cytokines on the move and following homing and incorporating into the integral components of the organ, interact with cell/cell products which leads to inducing specific activation signaling patterns and ultimately dictating MSC phenotype [ 3 – 5 ]. Naïve MSCs can be altered in their properties and converted into pro/anti-inflammatory population cells.…”

Section: Introductionmentioning

confidence: 99%

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A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

Hoseinzadeh,

Mahmoudi,

Rafatpanah

et al. 2023

Stem Cell Res Ther

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Background Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease. Methods Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons. Results Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation. Conclusions Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties. Graphical abstract

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Section: Methodsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

Hoseinzadeh,

Mahmoudi,

Rafatpanah

et al. 2023

Stem Cell Res Ther

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“…Also, it has been claimed that the level of iTreg is reduced in SLE. This type of Treg is produced by altering the CD4+CD25 − T cells to CD4 + CD25 + foxp3 + T cells 46,84 . Similarly, the expression level of B7 molecules may contribute to the pathogenesis of SLE due to the inability to increase the amount of B7 when dealing with pathogens.…”

Section: The Role Of Ctla–cd80/86 Interaction In Autoimmune Diseasesmentioning

confidence: 99%

“…This type of Treg is produced by altering the CD4+CD25 − T cells to CD4 + CD25 + foxp3 + T cells. 46,84 Similarly, the expression level of B7 molecules may contribute to the pathogenesis of SLE due to the inability to increase the amount of B7 when dealing with pathogens. In detail, T lymphocyte of SLE patients has a defect in proliferation due to the dysfunction of DC in the upregulation of B7 molecules in exposure to mitogens, suggestive of dysfunction of this pathway in SLE.…”

Section: Slementioning

confidence: 99%

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Darvish,

Kheder,

Faraj

et al. 2023

Cell Biochemistry & Function

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Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self‐tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4–CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4–CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4–CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4–CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases.

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Gingival mesenchymal stem cell therapy, immune cells, and immunoinflammatory application

Tolouei,

Oruji,

Tehrani

et al. 2023

Mol Biol Rep

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Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

Cited by 4 publications

References 170 publications

A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Gingival mesenchymal stem cell therapy, immune cells, and immunoinflammatory application

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