Mesenchymal Stem Cells Inhibit the Differentiation of CD4+ T Cells into Interleukin-17-Secreting T Cells

Purpose: Promising advances have been made in mesenchymal stem cell transplantation to re-induce the immune tolerance in neuroinflammatory animal models and Multiple Sclerosis patients. The available evidence demonstrated that immunomodulatory effects of mesenchymal stem cell are particularly exerted through releasing exosomes to their environment. We therefore, aimed to comparatively assess the potential effect of mesenchymal stem cells and mesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting Multiple Sclerosis patients. Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their anti-inflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, and interleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals. Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy control: p<0.001) and interleukin-17 (healthy control: p<0.001, MS patients: p<0.001), with a significant increase of IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derived exosomes demonstrated higher immune-modulating properties on conventional T cells responses, compared to MSCs. Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy. In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics, could be considered as an alternative for Mesenchymal stem cells in treating multiple sclerosis.

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Interferon-gamma and Interleukin-17 Modified Mesenchymal Stem Cells (MSC) Directly or Indirectly Modulate T Cell Responses By Expressing Inhibitory Factors, Downregulating T Cell Activation and Inducing Regulatory T Cells.

Transplantation Journal ◽

10.1097/00007890-201407151-00146 ◽

2014 ◽

Vol 98 ◽

pp. 43

Author(s):

K. Sivanathan ◽

C. Hope ◽

D. Rojas-Canales ◽

R. Carroll ◽

S. Gronthos ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

T Cell ◽

Regulatory T Cells ◽

Interferon Gamma ◽

T Cell Activation ◽

Cell Activation ◽

Interleukin 17 ◽

Cell Responses

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Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

Experimental and Therapeutic Medicine ◽

10.3892/etm.2017.4952 ◽

2017 ◽

Vol 14 (4) ◽

pp. 3541-3548 ◽

Cited By ~ 2

Author(s):

Zhou Xin Yang ◽

Ying Chi ◽

Yue Ru Ji ◽

You Wei Wang ◽

Jing Zhang ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Cd4 T Cells ◽

Human Umbilical Cord ◽

Interleukin 9

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IDO and CD40 May Be Key Molecules for Immunomodulatory Capacity of the Primed Tonsil-Derived Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115772 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5772

Author(s):

Hyun-Joo Lee ◽

Harry Jung ◽

Dong-Kyu Kim

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Cd4 T Cells ◽

Immune Cell ◽

Suppressive Effect ◽

Tnf Α ◽

Immunomodulatory Capacity ◽

Ifn Γ

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4+ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.

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