Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE

Simple item page
dc.contributor.authorKurte, Mónica
dc.contributor.authorVega-Letter, Ana María
dc.contributor.authorLuz-Crawford, Patricia
dc.contributor.authorDjouad, Farida
dc.contributor.authorNoël, Danièle
dc.contributor.authorKhoury, Maroun
dc.contributor.authorCarrión, Flavio
dc.date.accessioned2021-08-11T22:41:47Z
dc.date.available2021-08-11T22:41:47Z
dc.date.issued2020
dc.description.abstractBackground: Mesenchymal stem cells (MSCs) have been recognized for their regenerative and anti-inflammatory capacity which makes them very attractive to cell therapy, especially those ones to treat inflammatory and autoimmune disease. Two different immune-phenotypes have been described for MSCs depending on which Tolllike receptor (TLR) is activated. MSC1 is endowed with a pro-inflammatory phenotype following TLR4 activation with LPS. On the other hand, anti-inflammatory MSC2 is induced by the activation of TLR3 with Poly(I:C). High immunoplasticity of MSCs is a matter of concern in cell-based therapies. In this study, we investigated whether a single stimulus can induce both types of MSCs through a differential activation of TLR4 with LPS. Methods: MSCs were activated with LPS following a short exposure of 1-h (MSCs-LPS1h) or long-time exposure for 48 h (MSCs-LPS48h), and then, we evaluated the biological response in vitro, the immunosuppressive capacity of MSCs in vitro, and the therapeutic potential of MSCs in an experimental autoimmune encephalomyelitis (EAE) mouse model. Results: Our results showed that 1-h LPS exposure induced a MSC1 phenotype. Indeed, MSCs-LPS1h expressed low levels of NO/iNOS and decreased immunosuppressive capacity in vitro without therapeutic effect in the EAE model. In contrast, MSCs-LPS48h achieved a MSC2-like phenotype with significant increase in the immunosuppressive capacity on T cell proliferation in vitro, together with an improved in the therapeutic effect and higher Treg, compared to unstimulated MSCs. Furthermore, we determine through the MSCs-TLR4KO that the expression of TLR4 receptor is essential for MSCs’ suppressive activity since TLR4 deletion was associated with a diminished suppressive effect in vitro and a loss of therapeutic effect in vivo. Conclusions: We demonstrate that MSCs display a high immunoplasticity commanded by a single stimulus, where LPS exposure time regulated the MSC suppressive effect leading into either an enhanced or an impairment therapeutic activity. Our results underscore the importance of phenotype conversion probably related to the TLR4 expression and activation, in the design of future clinical protocols to treat patients with inflammatory and autoimmune diseases.es
dc.identifier.citationStem Cell Research & Therapy, 2020, vol.11:416es
dc.identifier.urihttps://doi.org/10.1186/s13287-020-01840-2es
dc.identifier.urihttp://hdl.handle.net/11447/4291
dc.language.isoenes
dc.subjectMSCses
dc.subjectTLR4es
dc.subjectLPSes
dc.subjectImmunosuppressiones
dc.subjectCell plasticityes
dc.subjectAutoimmune diseaseses
dc.titleTime-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAEes
dc.typeArticlees

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE.pdf
Size:
2.4 MB
Format:
Adobe Portable Document Format
Description:
Texto completo
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services