PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties.

Tytuł:: PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties.
Autorzy:: Contreras-Lopez RA; Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.; IRMB, Univ Montpellier, INSERM, CHU Montpellier, Inserm U 1183, IRMB, Hôpital Saint-Eloi, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France.
Elizondo-Vega R; Facultad de Ciencias Biológicas, Departamento de Biología Celular, Laboratorio de Biología Celular, Universidad de Concepción, Concepción, Chile.
Torres MJ; Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaiso, Valparaiso, Chile.
Vega-Letter AM; Cells for Cells, Consorcio Regenero, Las Condes, Santiago, Chile.; Laboratory of Nano-Regenerative Medicine, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.
Luque-Campos N; Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.
Paredes-Martinez MJ; Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.
Pradenas C; Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.
Tejedor G; IRMB, Univ Montpellier, INSERM, CHU Montpellier, Inserm U 1183, IRMB, Hôpital Saint-Eloi, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France.
Oyarce K; Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile.
Salgado M; Facultad de Ciencias Biológicas, Departamento de Biología Celular, Laboratorio de Biología Celular, Universidad de Concepción, Concepción, Chile.
Jorgensen C; IRMB, Univ Montpellier, INSERM, CHU Montpellier, Inserm U 1183, IRMB, Hôpital Saint-Eloi, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France.
Khoury M; Cells for Cells, Consorcio Regenero, Las Condes, Santiago, Chile.; Laboratory of Nano-Regenerative Medicine, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.
Kronke G; Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054, Erlangen, Germany.
Garcia-Robles MA; Facultad de Ciencias Biológicas, Departamento de Biología Celular, Laboratorio de Biología Celular, Universidad de Concepción, Concepción, Chile.
Altamirano C; Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaiso, Valparaiso, Chile.
Luz-Crawford P; Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile. .
Djouad F; IRMB, Univ Montpellier, INSERM, CHU Montpellier, Inserm U 1183, IRMB, Hôpital Saint-Eloi, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France. .
Źródło:: Scientific reports [Sci Rep] 2020 Jul 10; Vol. 10 (1), pp. 11423. Date of Electronic Publication: 2020 Jul 10.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Mesenchymal Stem Cells/*metabolism
PPAR-beta/*metabolism
Receptors, Cytoplasmic and Nuclear/*metabolism
Animals ; Bone Marrow Cells/cytology ; CD4-Positive T-Lymphocytes/cytology ; Cell Proliferation ; Gene Silencing ; Glycolysis ; Immunosuppression Therapy ; Mice ; Oligomycins/chemistry ; Th1 Cells/cytology ; Th17 Cells/cytology
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Substance Nomenclature:: 0 (Oligomycins)
0 (PPAR-beta)
0 (Ppard protein, mouse)
0 (Receptors, Cytoplasmic and Nuclear)
Entry Date(s):: Date Created: 20200712 Date Completed: 20210111 Latest Revision: 20211204
Update Code:: 20240105
PubMed Central ID:: PMC7351754
DOI:: 10.1038/s41598-020-68347-x
PMID:: 32651456
: Czasopismo naukowe

Pełny tekst

Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARβ/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARβ/δ on MSC metabolic activity and the relevance of PPARβ/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARβ/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARβ/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARβ/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.

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