ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 60

Combined Inhibition of Mechanistic Target of Rapamycin and Glutamine Metabolism Inhibits CD4 T Cell Proliferation and Th17 Differentiation, Facilitates the Expansion of Myeloid-Derived Suppressor Cells, and Synergistically Ameliorates Arthritis in SKG Mice

Yo Ueda1, Jun Saegusa1, Tadashi Okano2, Sho Sendo1, Hirotaka Yamada2, Kengo Akashi1, Akira Onishi1 and Akio Morinobu1, 1Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan, 2Rheumatology and Clinical immunology, Kobe University Graduate School of Medicine, Kobe, Japan

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: combination therapies, mTor and metabolism

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Sunday, October 21, 2018

Session Title: Rheumatoid Arthritis – Animal Models Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: The mechanistic target of rapamycin (mTOR) pathway and glutamine metabolism are activated cooperatively in the differentiation and the activation of inflammatory immune cells such as effector lymphocytes and M1 macrophages. Myeloid-derived suppressor cells (MDSCs) are an immature myeloid cell population with immunosuppressive ability. The promotion of the expansion and immunosuppressive ability of MDSCs by mTOR inhibition has been reported. The aim of this study is to elucidate the effect of combined inhibition of mTOR and glutamine metabolism on immune cells and therapeutic effect in a mouse model of rheumatoid arthritis.

Methods: The proliferation of CD4+ T cells treated with four patterns of drugs; 1) DMSO (control), 2) rapamycin (Rapa), 3) 6-Diazo-5-oxo-L-norleucine (DON; a glutamine antagonist), or 4) the combination of rapamycin and DON (Rapa+DON), were assessed by CFSE-dilution assay. The differentiation of CD4+ T cells and bone marrow cells from untreated Balb/c mice were analyzed by flow cytometry. Immunosuppressive ability of in vitro generated-MDSCs were assessed by co-culture with CFSE-labeled CD4+ T cells. The four patterns of drugs were administered intraperitoneally to arthritic SKG mice and splenocytes were analyzed by flow cytometry.

Results: Rapamycin and DON synergistically inhibited the CD4+ T cell proliferation and both of them inhibited the Th17 cell differentiation in vitro. DON significantly suppressed the differentiation of dendritic cells and macrophages, and increased the proportions of MDSCs in vitro. Most of in vitro generated-MDSCs treated with rapamycin or DON were Ly6G+ granulocytic (G)-MDSCs. On the other hand, in vitro-generated G-MDSCs treated with rapamycin suppressed the proliferation of CD4+ T cells more strongly than G-MDSCs treated without rapamycin. The combination of rapamycin and DON synergistically suppressed arthritis in SKG mice in vivo (see Figure). The number of CD4+ T cells in splenocytes was the most suppressed in the combination therapy group and the proportions of Th17 cell were suppressed in rapamycin, DON, or the combination therapy groups.

Conclusion: The combination of rapamycin and DON synergistically ameliorated arthritis in SKG mice possibly through suppressing CD4+ T cell proliferation and Th17 differentiation.


Disclosure: Y. Ueda, None; J. Saegusa, None; T. Okano, None; S. Sendo, None; H. Yamada, None; K. Akashi, None; A. Onishi, None; A. Morinobu, None.

To cite this abstract in AMA style:

Ueda Y, Saegusa J, Okano T, Sendo S, Yamada H, Akashi K, Onishi A, Morinobu A. Combined Inhibition of Mechanistic Target of Rapamycin and Glutamine Metabolism Inhibits CD4 T Cell Proliferation and Th17 Differentiation, Facilitates the Expansion of Myeloid-Derived Suppressor Cells, and Synergistically Ameliorates Arthritis in SKG Mice [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/combined-inhibition-of-mechanistic-target-of-rapamycin-and-glutamine-metabolism-inhibits-cd4-t-cell-proliferation-and-th17-differentiation-facilitates-the-expansion-of-myeloid-derived-suppressor-cell/. Accessed January 27, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/combined-inhibition-of-mechanistic-target-of-rapamycin-and-glutamine-metabolism-inhibits-cd4-t-cell-proliferation-and-th17-differentiation-facilitates-the-expansion-of-myeloid-derived-suppressor-cell/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.