Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms
Abstract Dysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory re...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-93025-x |
| _version_ | 1818996806599573504 |
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| author | Alice Valentin-Torres Cora Day Jennifer M. Taggart Nicholas Williams Samantha R. Stubblefield Valerie D. Roobrouck Jelle Beyens Anthony E. Ting |
| author_facet | Alice Valentin-Torres Cora Day Jennifer M. Taggart Nicholas Williams Samantha R. Stubblefield Valerie D. Roobrouck Jelle Beyens Anthony E. Ting |
| author_sort | Alice Valentin-Torres |
| collection | DOAJ |
| description | Abstract Dysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory responses in a variety of clinical conditions including acute ischemic stroke, acute myocardial infarction (AMI), graft vs host disease (GvHD), and acute respiratory distress syndrome (ARDS). One of the proposed mechanisms by which MAPC cells modulate immune responses is via the induction of regulatory T cells (Tregs), however, the mechanism(s) involved remains to be fully elucidated. Herein, we demonstrate that, in an in vitro setting, MAPC cells increase Treg frequencies by promoting Treg proliferation and CD4+ T cell differentiation into Tregs. Moreover, MAPC cell-induced Tregs (miTregs) have a more suppressive phenotype characterized by increased expression of CTLA-4, HLA-DR, and PD-L1 and T cell suppression capacity. MAPC cells also promoted Treg activation by inducing CD45RA+ CD45RO+ transitional Tregs. Additionally, we identify transforming growth factor beta (TGFβ) as an essential factor for Treg induction secreted by MAPC cells. Furthermore, inhibition of indoleamine 2, 3-dioxygenase (IDO) resulted in decreased Treg induction by MAPC cells demonstrating IDO involvement. Our studies also show that CD14+ monocytes play a critical role in Treg induction by MAPC cells. Our study describes MAPC cell dependent Treg phenotypic changes and provides evidence of potential mechanisms by which MAPC cells promote Treg differentiation. |
| first_indexed | 2024-12-20T21:35:36Z |
| format | Article |
| id | doaj.art-779477ab8c53409695514d59b74870eb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:35:36Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-779477ab8c53409695514d59b74870eb2022-12-21T19:25:57ZengNature PortfolioScientific Reports2045-23222021-06-0111111610.1038/s41598-021-93025-xMultipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanismsAlice Valentin-Torres0Cora Day1Jennifer M. Taggart2Nicholas Williams3Samantha R. Stubblefield4Valerie D. Roobrouck5Jelle Beyens6Anthony E. Ting7Athersys, Inc. ClevelandAthersys, Inc. ClevelandAthersys, Inc. ClevelandAthersys, Inc. ClevelandAthersys, Inc. ClevelandReGenesys BVReGenesys BVAthersys, Inc. ClevelandAbstract Dysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory responses in a variety of clinical conditions including acute ischemic stroke, acute myocardial infarction (AMI), graft vs host disease (GvHD), and acute respiratory distress syndrome (ARDS). One of the proposed mechanisms by which MAPC cells modulate immune responses is via the induction of regulatory T cells (Tregs), however, the mechanism(s) involved remains to be fully elucidated. Herein, we demonstrate that, in an in vitro setting, MAPC cells increase Treg frequencies by promoting Treg proliferation and CD4+ T cell differentiation into Tregs. Moreover, MAPC cell-induced Tregs (miTregs) have a more suppressive phenotype characterized by increased expression of CTLA-4, HLA-DR, and PD-L1 and T cell suppression capacity. MAPC cells also promoted Treg activation by inducing CD45RA+ CD45RO+ transitional Tregs. Additionally, we identify transforming growth factor beta (TGFβ) as an essential factor for Treg induction secreted by MAPC cells. Furthermore, inhibition of indoleamine 2, 3-dioxygenase (IDO) resulted in decreased Treg induction by MAPC cells demonstrating IDO involvement. Our studies also show that CD14+ monocytes play a critical role in Treg induction by MAPC cells. Our study describes MAPC cell dependent Treg phenotypic changes and provides evidence of potential mechanisms by which MAPC cells promote Treg differentiation.https://doi.org/10.1038/s41598-021-93025-x |
| spellingShingle | Alice Valentin-Torres Cora Day Jennifer M. Taggart Nicholas Williams Samantha R. Stubblefield Valerie D. Roobrouck Jelle Beyens Anthony E. Ting Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms Scientific Reports |
| title | Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms |
| title_full | Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms |
| title_fullStr | Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms |
| title_full_unstemmed | Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms |
| title_short | Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms |
| title_sort | multipotent adult progenitor cells induce regulatory t cells and promote their suppressive phenotype via tgfβ and monocyte dependent mechanisms |
| url | https://doi.org/10.1038/s41598-021-93025-x |
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