Investigation of the effect of IFN-γ/TNF-α-treated mesenchymal stem cells on Th9- and Treg cell-related parameters in a mouse model of ovalbumin-induced allergic asthma

Nozari, Parvin; Mokhtari, Pejman; Nemati, Maryam; Zainodini, Nahid; Taghipour, Zahra; Asadi, Fatemeh; Ayoobi, Fatemeh; Jafarzadeh, Abdollah

doi:10.1080/08923973.2022.2082977

Cited by 4 publications

(6 citation statements)

References 61 publications

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“…2, the result of flow cytometry showed that these cells were positive for CD73 (99.6 %), CD90 (84.6 %) and CD105 (99.0 %) markers, and negative for CD34 (0.548 %), CD45 (0.670 %) markers. Similar to our studies, in other studies up to three positive surface markers and up to two negative surface markers were used to characterize MSCs [35,43,44].…”

Section: Resultssupporting

confidence: 79%

“…The results from an in vitro experiment also indicated that IFN-γ promotes the capacity MSCs to induce Treg cell differentiation [55]. The enhancing effects of the treatment with IFN-γinduced MSCs on the expression of Treg cell-related markers were also observed in a mouse model of allergic asthma [35]. The greater expression of CCR4 and its ligand, CCL22, can lead to the larger accumulation of the Treg and Th2 cells in the CNS.…”

Section: Discussionmentioning

confidence: 86%

“…The harvested cells were transferred into the new flasks and expanded for further characterization or treated with 10 ng/ml recombinant mouse IFN-γ (for 48 h) as a stimulant of immunomodulatory functions of MSCs [33]. The dose of IFN-γ and the number of the infused MSCs were determined according to the previous experiments [33][34][35][36][37]. Wang et al [38] reported that the long-time incubation with high IFN-γ doses suppressed MSCs-induced immunomodulatory activities.…”

Section: Isolation Culturing and Treatment Of Adipose Tissuederived M...mentioning

confidence: 99%

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Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis

et al. 2023

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Background Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model. Material and Methods EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs. The EAE manifestations were registered daily and finally, the brain and spinal cords were isolated for histopathological and gene expression studies. Results The clinical scores were lowered in MSCs and IFN-γ-licensed MSCs groups, however, mice treated with IFN-γ-licensed MSCs exhibited lower clinical scores than MSCs-treated mice. Leukocyte inﬁltration into the brain was reduced after treatment with MSCs or IFN-γ-licensed MSCs compared to untreated group (P<0.05 and P<0.01, respectively). In comparison with untreated EAE mice, treatment with MSCs reduced CCL20 expression (P<0.001) and decreased CXCR3 and CCR6 expression (P<0.02 and P<0.04, respectively). In comparison with untreated EAE mice, treatment with IFN-γ-licensed MSCs reduced CXCL10, CCL17 and CCL20 expression (P<0.05, P<0.05, and P<0.001, respectively) as well as decreased CXCR3 and CCR6 expression (P<0.002 and P<0.02, respectively), whilst promoting expression of CCL22 and its receptor CCR4 (P<0.0001 and P<0.02, respectively). In comparison with MSC-treated group, mice treated with IFN-γ-licensed MSCs exhibited lower CXCL10 and CCR6 expression (P<0.002 and P<0.01, respectively), whereas greater expression of CCL22 and CCR4 (P<0.0001 and P<0.01, respectively). Conclusion Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.

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Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 86%

Section: Isolation Culturing and Treatment Of Adipose Tissuederived M...mentioning

confidence: 99%

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Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis

et al. 2023

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“…Previous studies have reported that Treg upregluation may be the mechanism behind the inhibitory effects of intravenously administered ucMSCs on the Th2 response 22 . MSCs treated with IFN-γ/TNF-α showed the modulating effect on Th9 cells contributing to the development of allergy by involving ILC2 activation, IgE production, eosinophil recruitment into airway 30 – 33 . MSCs indirectly enhance IL-10 release by alternatively activated macrophages as well as inducing Tregs.…”

Section: Discussionmentioning

confidence: 99%

Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects

Kang

Bang

et al. 2022

Sci Rep

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Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF+CD11c+CD11b- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

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“…MSCs can downregulate local inflammatory responses, reduce inflammatory damage, and reverse airway remodeling by restoring the Th1/Th2 balance 10 , reverse the Th17/Tregs imbalance 52 , inhibit DC maturation and antigen presentation 78 , suppress the degranulation response of MCs 79 , restrain innate lymphoid cell group 2 (ILC2)-mediated pathology 80 , promote the shift of M1 macrophages to M2 macrophages 57 , induce the differentiation of Treg cells 81 , and repair epithelial injury 19 through paracrine secretion or direct cell–cell contact ( Fig. 1 ).…”

Section: Msc-based Therapy For Asthmamentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

Huang

Zeng

et al. 2023

Cell Transplant

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Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro, and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.

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Investigation of the effect of IFN-γ/TNF-α-treated mesenchymal stem cells on Th9- and Treg cell-related parameters in a mouse model of ovalbumin-induced allergic asthma

Cited by 4 publications

References 61 publications

Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis

Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis

Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects

Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

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