ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 931

mTOR Complex 1 Signaling Is Required for the Steady-State in Vivo Development of Inflammatory Monocytes

Pui Y. Lee1, David Sykes2, Sarah Ameri3, Allyn Morris4 and Peter A. Nigrovic5, 1Division of Immunology, Boston Children's Hospital, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 4Brigham and Women's Hospital, Boston, MA, 5Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Inflammation, mTor and monocytes

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

Date: Sunday, November 8, 2015

Title: Innate Immunity and Rheumatic Disease

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Monocytes and macrophages are essential to innate immunity but also propagate the inflammatory response in autoimmune arthritis and lupus nephritis.  Spontaneous development of inflammatory monocytes (Ly6Chi CCR2+) and subsequent differentiation to residential monocytes (Ly6Clo CX3CR1hi) from murine bone marrow precursor cells is an enigmatic process that involves numerous transcription factors.  Understanding the signaling pathways involved in myeloid development could help identify novel treatment targets for inflammatory diseases.  

Methods: We developed a murine myeloid progenitor cell line with CCR2RFP CX3CR1GFP reporters to track monocyte differentiation.  Small molecule library screen was used to identify biological pathways involved in monocyte development.  Activation of mTOR substrates was measured by intracellular flow cytometry.  Key findings were confirmed using pharmacologic inhibition and genetic disruption.

Results: Using a novel progenitor cell line that recapitulates the monocyte development continuum, we identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) on the generation of inflammatory monocyte through a small molecule library screen.  Basal mTORC1 signaling was more prominent in monocytes than other cell subsets in wild-type mice and humanized mice.  Inhibition of mTORC1 by rapamycin or disruption of Raptor (an essential component of mTORC1) impaired monocyte development, while deletion of TSC-1 (a negative regulator of mTORC1) accelerated the differentiation into mature macrophages.  Correspondingly, Raptor fl/fl UBC-cre/ERT2 mice susceptible to tamoxifen-mediated deletion of Raptor demonstrated a rapid, inducibe depletion of circulating inflammatory monocytes, confirm an essential non-redundant role of mTORC1 in monocyte development in vivo. Curiously, Raptor-deficient progenitors in the bone marrow spontaneously differentiated into Ly6Clo CX3CR1low myeloid cells with characteristics of alternatively-activated macrophages.   

Conclusion: Using a combination of in vitro and in vivo approaches, we identified a previously unrecognized role of mTORC1 in the normal development of inflammatory monocytes.  These findings support the potential utility of mTORC1 inhibitors in monocyte- and macrophage-mediated inflammatory diseases.


Disclosure: P. Y. Lee, None; D. Sykes, None; S. Ameri, None; A. Morris, None; P. A. Nigrovic, None.

To cite this abstract in AMA style:

Lee PY, Sykes D, Ameri S, Morris A, Nigrovic PA. mTOR Complex 1 Signaling Is Required for the Steady-State in Vivo Development of Inflammatory Monocytes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/mtor-complex-1-signaling-is-required-for-the-steady-state-in-vivo-development-of-inflammatory-monocytes/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/mtor-complex-1-signaling-is-required-for-the-steady-state-in-vivo-development-of-inflammatory-monocytes/

Advanced Search

Your Favorites

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

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology