| Author | Du-Rocher, Bárbara | |
| Author | Binato, Renata | |
| Author | Freitas Junior, Julio Cesar Madureira de | |
| Author | Corrêa, Stephany | |
| Author | Mencalha, André Luiz | |
| Author | Morgado-Díaz, José Andrés | |
| Author | Abdelhay, Eliana Saul Furquim Werneck | |
| Access date | 2021-01-10T18:23:40Z | |
| Available date | 2021-01-10T18:23:40Z | |
| Document date | 2020 | |
| Citation | DU-ROCHER, Bárbara et al. IL-17 Triggers Invasive and Migratory Properties in Human MSCs, while IFNy Favors their Immunosuppressive Capabilities: Implications for the “Licensing” Process. Stem Cell Reviews and Reports, v. 16,p. 1266-1279, Oct. 2020. | pt_BR |
| ISSN | 1550-8943 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45551 | |
| Language | eng | pt_BR |
| Publisher | Springer | pt_BR |
| Rights | open access | |
| Subject in Portuguese | IFNy | pt_BR |
| Subject in Portuguese | Células estromais mesenquimais (MSCs) | pt_BR |
| Subject in Portuguese | Matriz de chips | pt_BR |
| Subject in Portuguese | IL-17 | pt_BR |
| Subject in Portuguese | Imunomodulação | pt_BR |
| Title | IL-17 Triggers Invasive and Migratory Properties in Human MSCs, while IFNy Favors their Immunosuppressive Capabilities: Implications for the “Licensing” Process | pt_BR |
| Type | Article | |
| DOI | 10.1007/s12015-020-10051-4 | |
| Abstract | Mesenchymal stromal cells (MSCs) were first used as a source for cell therapy in 1995; however, despite their versatility and
unambiguous demonstration of efficacy and safety in preclinical/phase I studies, the positive effect of MSCs in human phase III
studies did not resemble the success obtained in mouse models of disease. This dissonance highlights the need to more thoroughly
study the immunobiology of MSCs to make better use of these cells. Thus, we aimed to study the immunobiology of
MSCs by using chip array analysis as a method for general screening to obtain a global picture in our model study and found
IFNy and IL-17 signaling as the first two “top canonical pathways” involved in MSCs immunomodulation. The role of IFNy in
triggering the immunosuppressive properties of MSCs is well recognized by many groups; however, the role of IL-17 in this
process remains uncertain. Interestingly, in contrast to IFNy, which actively improved the MSCs-mediated immunosuppression,
IL-17 did not improve directly the MSCs-mediated immunosuppression. Instead, IL-17 signaling induced the migration ofMSCs
and inflammatory cells, bringing these cell types together and increasing the likelihood of the lymphocytes sensing the immunosuppressive
molecules produced by the MSCs. These effects also correlated with high levels of cytokine/chemokine production
and metalloprotease activation by MSCs. Importantly, this treatment maintained the MSCs safety profile by not inducing the
expression of molecules related to antigen presentation. In this way, our findings highlight the possibility of using IL-17, in
combination with IFNy, to prime MSCs for cell therapy to improve their biological properties and thus their therapeutic efficacy.
Finally, the use of preactivated MSCs may also minimize variations among MSCs to produce more uniformtherapeutic products.
In the not-so-distant future, we envisage a portfolio of MSCs activated by different cocktails specifically designed to target and
treat specific diseases. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Centro de Transplante de Medula óssea. Laboratório de Células-tronco. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Centro de Transplante de Medula óssea. Laboratório de Células-tronco. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Programa de Oncobiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Centro de Transplante de Medula óssea. Laboratório de Células-tronco. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro. Instituto de Biofísica e Biometria. Laboratório de Biologia do Câncer. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Programa de Oncobiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Centro de Transplante de Medula óssea. Laboratório de Células-tronco. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Mesenchymal stromal cells (MSCs) | pt_BR |
| Subject | IFNy | pt_BR |
| Subject | IL-17 | pt_BR |
| Subject | Chip array | pt_BR |
| Subject | Immunomodulation | pt_BR |
