ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

PI3Kα and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization

E. Kefalogianni,1 M. Mounayar,2 B. Smith,2 J. Azzi,2 L. Chabtini,2 P. Fiorina,2 M. Kraus,3 R. Briddell,4 W. Fodor,5 A. Herrlich,1 R. Abdi.2

1Brigham and Women's Hospital, Harvard Medical School, Boston, MA
2Transplantation Research Center, Brigham and Women's and Children's Hospital, Harvard Medical School, Boston, MA
3Viacord LLC, a PerkinElmer Company, Cambridge, MA
4ViaCord Processing Lab, Viacord LLC, a PerkinElmer Company, Hebron, KY
5The Cell Therapy Group, Madison, CT.

Meeting: 2015 American Transplant Congress

Abstract number: A241

Keywords: Immunosuppression, Interferon (IFN), Stem cells, T cells

Session Information

Session Name: Poster Session A: Preclinical Immunosuppression and Tolerance

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

The immunomodulatory capacity of mesenchymal stem cells (MSC) is critical for their use in therapeutic applications. MSC response to specific inflammatory cues allows them to switch between a pro-inflammatory (MSC1) or anti-inflammatory (MSC2) phenotype. Regulatory mechanisms controlling this switch remain to be defined. One characteristic feature of MSC2 is their ability to respond to IFNγ with induction of Indoleamine 2,3-dioxygenase (IDO), representing the key immunoregulatory molecule released by human MSC. Here we show that STAT1 and PI3Kα pathways interplay regulates IFNγ-induced IDO production in MSC. Chemical PI3K pan-inhibition, PI3Kα-specific inhibition or shRNA knockdown diminished IFNγ-induced IDO production. This effect involved PI3Kα-mediated upregulation of STAT1 protein levels and phosphorylation at Ser727. Overexpression of STAT1 or of a constitutively active PI3Kα mutant failed to induce basal IDO production, but shifted MSC into an MSC2-like phenotype by strongly enhancing IDO production in response to IFNγ as compared to controls. Finally, downregulation of STAT1 abrogated the immunosuppressive capacity of MSC in a T-cell suppression assay, while STAT1 overexpression significantly enhanced it. Our results for the first time identify critical upstream signals for the induced production of IDO in MSCs that could be manipulated therapeutically to enhance the immunosuppressive MSC2 phenotype.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Kefalogianni E, Mounayar M, Smith B, Azzi J, Chabtini L, Fiorina P, Kraus M, Briddell R, Fodor W, Herrlich A, Abdi R. PI3Kα and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/pi3k-and-stat1-interplay-regulates-human-mesenchymal-stem-cell-immune-polarization/. Accessed May 30, 2025.

« Back to 2015 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences