Theranostics 2018; 8(3):846-859. doi:10.7150/thno.21793 This issue Cite

Research Paper

Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay

Patricia Luz-Crawford1,4, Gabriel Espinosa-Carrasco1#, Natacha Ipseiz7#, Rafael Contreras1,4, Gautier Tejedor1, Daniel A. Medina5, Ana-Maria Vega-Letter6, Devi Ngo3, Eric F. Morand3, Jérôme Pène1, Javier Hernandez1*, Christian Jorgensen1,2*, Farida Djouad1✉

1. IRMB, INSERM, Université Montpellier, Montpellier, France
2. Service d'Immuno-Rhumatologie, Hôpital Lapeyronie, Montpellier, France
3. School of Clinical Sciences, Monash University, Melbourne, Australia
4. Facultad de Medicina, Universidad de los Andes, Santiago, Chile
5. Department of Chemical and Bioprocess Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile
6. Clinica Alemana Universidad del Desarrollo, Santiago, Chile
7. Cardiff University School of Medicine, United Kingdom.
# Equally contributing authors
* Equally contributing authors

Citation:
Luz-Crawford P, Espinosa-Carrasco G, Ipseiz N, Contreras R, Tejedor G, Medina DA, Vega-Letter AM, Ngo D, Morand EF, Pène J, Hernandez J, Jorgensen C, Djouad F. Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics 2018; 8(3):846-859. doi:10.7150/thno.21793. https://www.thno.org/v08p0846.htm
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Abstract

Graphic abstract

Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive.

Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC. Adoptive transfer experiments sustained this Gilz-dependent suppressive effect of MSC on Th1 and Th17 cell functions. In immunoregulatory MSC, obtained by priming with IFN-γ and TNF-α, Gilz was translocated to the nucleus and bound to the promoters of inos and Activin βA to induce their expression. The increased expression of Activin A directly impacted on Th17 cells fate by repressing their differentiation program through the activation of Smad3/2 and enhancing IL-10 production.

Conclusion Our results reveal how Gilz controls inos and Activin βA gene expression to ultimately assign immunoregulatory status to MSC able to repress the pathogenic Th17 cell differentiation program and uncover Activin A as a novel mediator of MSC in this process.

Keywords: Mesenchymal Stem Cells, Gilz, Activin A, Th17 cells, Immunosuppression.


Citation styles

APA
Luz-Crawford, P., Espinosa-Carrasco, G., Ipseiz, N., Contreras, R., Tejedor, G., Medina, D.A., Vega-Letter, A.M., Ngo, D., Morand, E.F., Pène, J., Hernandez, J., Jorgensen, C., Djouad, F. (2018). Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics, 8(3), 846-859. https://doi.org/10.7150/thno.21793.

ACS
Luz-Crawford, P.; Espinosa-Carrasco, G.; Ipseiz, N.; Contreras, R.; Tejedor, G.; Medina, D.A.; Vega-Letter, A.M.; Ngo, D.; Morand, E.F.; Pène, J.; Hernandez, J.; Jorgensen, C.; Djouad, F. Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics 2018, 8 (3), 846-859. DOI: 10.7150/thno.21793.

NLM
Luz-Crawford P, Espinosa-Carrasco G, Ipseiz N, Contreras R, Tejedor G, Medina DA, Vega-Letter AM, Ngo D, Morand EF, Pène J, Hernandez J, Jorgensen C, Djouad F. Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics 2018; 8(3):846-859. doi:10.7150/thno.21793. https://www.thno.org/v08p0846.htm

CSE
Luz-Crawford P, Espinosa-Carrasco G, Ipseiz N, Contreras R, Tejedor G, Medina DA, Vega-Letter AM, Ngo D, Morand EF, Pène J, Hernandez J, Jorgensen C, Djouad F. 2018. Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics. 8(3):846-859.

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