Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorCélula Mater-
Autor(es): dc.contributorHalpern Clinic-
Autor(es): dc.contributorCEERH-
Autor(es): dc.creatorPolonio, Carolina Manganeli-
Autor(es): dc.creatorde Freitas, Carla Longo-
Autor(es): dc.creatorde Oliveira, Marília Garcia-
Autor(es): dc.creatorRossato, Cristiano-
Autor(es): dc.creatorBrandão, Wesley Nogueira-
Autor(es): dc.creatorZanluqui, Nágela Ghabdan-
Autor(es): dc.creatorde Oliveira, Lilian Gomes-
Autor(es): dc.creatorNishiyama Mimura, Luiza Ayumi [UNESP]-
Autor(es): dc.creatorBarros Silva, Maysa Braga-
Autor(es): dc.creatorGarcia Calich, Vera Lúcia-
Autor(es): dc.creatorNisenbaum, Marcelo Gil-
Autor(es): dc.creatorHalpern, Silvio-
Autor(es): dc.creatorEvangelista, Lucila-
Autor(es): dc.creatorMaluf, Mariangela-
Autor(es): dc.creatorPerin, Paulo-
Autor(es): dc.creatorCzeresnia, Carlos Eduardo-
Autor(es): dc.creatorSchatzmann Peron, Jean Pierre-
Data de aceite: dc.date.accessioned2022-02-22T00:51:53Z-
Data de disponibilização: dc.date.available2022-02-22T00:51:53Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1042/CS20201544-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/207943-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/207943-
Descrição: dc.descriptionCellular therapy with mesenchymal stem cells (MSCs) is a huge challenge for scientists, as little translational relevance has been achieved. However, many studies using MSCs have proved their suppressive and regenerative capacity. Thus, there is still a need for a better understanding of MSCs biology and the establishment of newer protocols, or to test unexplored tissue sources. Here, we demonstrate that murine endometrial-derived MSCs (meMSCs) suppress Experimental Autoimmune Encephalomyelitis (EAE). MSC-treated animals had milder disease, with a significant reduction in Th1 and Th17 lymphocytes in the lymph nodes and in the central nervous system (CNS). This was associated with increased Il27 and Cyp1a1 expression, and presence of IL-10-secreting T CD4+ cells. At EAE peak, animals had reduced CNS infiltrating cells, histopathology and demyelination. qPCR analysis evidenced the down-regulation of several pro-inflammatory genes and up-regulation of indoleamine-2,3-dioxygenase (IDO). Consistently, co-culturing of WT and IDO-/- meMSCs with T CD4+ cells evidenced the necessity of IDO on the suppression of encephalitogenic lymphocytes, and IDO-/- meMSCs were not able to suppress EAE. In addition, WT meMSCs stimulated with IL-17A and IFN-γ increased IDO expression and secretion of kynurenines in vitro, indicating a negative feedback loop. Pathogenic cytokines were increased when CD4+ T cells from AhR-/- mice were co-cultured with WT meMSC. In summary, our research evidences the suppressive activity of the unexplored meMSCs population, and shows the mechanism depends on IDO-kynurenines-Aryl hydrocarbon receptor (AhR) axis. To our knowledge this is the first report evidencing that the therapeutic potential of meMSCs relying on IDO expression.-
Descrição: dc.descriptionNeuroimmune Interactions Laboratory Department of Immunology University of São Paulo (USP)-
Descrição: dc.descriptionImmunopathology and Allergy Post Graduate Program School of Medicine University of São Paulo (USP)-
Descrição: dc.descriptionInstitute of Biosciences UNESP-
Descrição: dc.descriptionClinical Biochemistry Laboratory Clinical Analysis Department University of São Paulo (USP)-
Descrição: dc.descriptionDepartment of Immunology Institute of Biomedical Sciences University of São Paulo (USP)-
Descrição: dc.descriptionDivision of Reproductive Medicine Célula Mater-
Descrição: dc.descriptionDivision of Reproductive Medicine Halpern Clinic-
Descrição: dc.descriptionDivision of Reproductive Medicine CEERH-
Descrição: dc.descriptionInstitute of Biosciences UNESP-
Formato: dc.format1065-1082-
Idioma: dc.languageen-
Relação: dc.relationClinical Science-
???dc.source???: dc.sourceScopus-
Título: dc.titleMurine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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