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: 1663

Age-Dependent Expansion and Activation of Disease-Associated Microglia in Neuropsychiatric Symptoms of Systemic Lupus Erythematosus

Hadijat Makinde1, Caroline Shah1, Miranda Gurra1, Yidan Wang1, Deborah Winter2 and Carla Cuda1, 1Northwestern University, Chicago, IL, 2Northwestern University, Skokie, IL

Meeting: ACR Convergence 2022

Keywords: genomics, innate immunity, Mouse Models, Lupus, Neuroimaging, neuropsychiatric disorders

  • 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: Monday, November 14, 2022

Title: Abstracts: SLE – Animal Models

Session Type: Abstract Session

Session Time: 10:30AM-11:30AM

Background/Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multipe end organs, including the brain. Despite a prevalence of over 50% in SLE patients depending on the attribution model, neuropsychiatric symptoms of SLE (NPSLE) are among the least understood complications. Notwithstanding the paucity of data examining underlying mechanisms, accumulating evidence points to microglia, the resident innate immune cells in the brain, as a driver of disease. Microglia are a heterogenous population and may exist as a homeostatic microglia or disease-associated microglia (DAM) state, the latter of which are associated with Alzheimer’s disease (AD). In AD, DAM co-localize with amyloid-b (Ab) plaques and may play a protective role in the early stages of AD by reducing Ab plaque burden. Our group was the first to show that microglial expression of DAM-associated genes correlates with the severity of hippocampal- and cerebellar-associated behavioral deficits in a NPSLE model prior to overt systemic disease. While DAM have been extensively studied in AD, to date no studies have specifically examined DAM in NPSLE.

Methods: Separate cohorts of female B6 and SLE-prone B6.Sle1Sle2Sle3 (B6.TC; Jackson #007228) mice underwent a battery of behavioral tasks at 2 months of age and 18F-FEPPA PET imaging targeting mitochondrial translocator protein-18 kDa (TSPO) in activated microglia at 11 months of age. Brains from additional cohorts were perfused and extracted, meninges were removed and live CD45+CD11b+ cells were FACSorted from pooled cell suspensions (n=3/strain/timepoint to account for biological variability; 2, 5, 8 and 11 months of age) for cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq; 10X Genomics 3′ v3.1). Data were analyzed in R using the Seurat package. Post-filtering, 10-12K cells/strain/timepoint were maintained.

Results: Similar to patients with NPSLE, B6.TC mice exhibit heightened anxiety and impaired motor learning indicative of amygdalar and cerebellar defects, respectively. We find that DAM in young B6.TC mice are enriched for genes involved in the response to IFN-γ. Activation of microglia by IFN-γ induces proinflammatory T cell-related chemokine genes as well as genes involved in antigen presentation; as a result, signals for T cell infiltration and antigen presentation are produced to allow for microglia-T cell interactions. Indeed, with age, B6.TC DAM expand and not only maintain enrichment of genes associated with the response to IFN-γ, but also adopt expression of genes involved in CD8 T cell activation and antigen presentation via MHC I and MHC II. Upregulation of Tspo expression in aged B6.TC DAM corresponds to increased 18F-FEPPA uptake in affected brain regions of B6.TC mice, suggesting regional microglial activation.

Conclusion: We find that DAM are somehow primed for activation early in NPSLE-like disease. With age, DAM expand and adopt a more activated phenotype, particularly suited for T cell interactions. Together, these discoveries are among the first to implicate DAM as a potentially pathogenic microglia subset in NPSLE. Future studies will investigate the initial source of IFN-γ.


Disclosures: H. Makinde, None; C. Shah, None; M. Gurra, None; Y. Wang, None; D. Winter, None; C. Cuda, None.

To cite this abstract in AMA style:

Makinde H, Shah C, Gurra M, Wang Y, Winter D, Cuda C. Age-Dependent Expansion and Activation of Disease-Associated Microglia in Neuropsychiatric Symptoms of Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/age-dependent-expansion-and-activation-of-disease-associated-microglia-in-neuropsychiatric-symptoms-of-systemic-lupus-erythematosus/. 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 ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/age-dependent-expansion-and-activation-of-disease-associated-microglia-in-neuropsychiatric-symptoms-of-systemic-lupus-erythematosus/

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