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: 1516

TSLP Upregulation in Human SSc Skin and Induction of Overlapping Profibrotic Genes and Intracellular Signaling with IL-13 and TGFb

Romy Christmann1, Allison Mathes2, Giuseppina Stifano2, Alsya J. Affandi3, Andreea Bujor3, Cristina Padilla3 and Robert Lafyatis3, 1Rheumatology, Boston University School of Medicine, Boston, MA, 2Rheumatology, Boston University Medical Center, Boston, MA, 3Rheumatology, Boston University, Boston, MA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Inflammation, macrophages and systemic sclerosis

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose:

to investigate the expression of Thymic Stromal Lymphopoietin (TSLP) in diffuse cutaneous systemic sclerosis (dcSSc) patients and explore its effects in vivo and in vitro comparing with IL-13 and TGF-beta stimulations. 

Methods:

Skin biopsies [dcSSc; n=13 and healthy controls (HC); n=12] were used for immunohistochemistry (IHC) and immunofluorescence studies using TSLP, CD4+, CD8+, CD31+, and CD163+ markers. Wild type (WT) and IL4Ra1-deficient mice (IL4Ra1-ko) were treated with TGF-beta, IL-13, Poly(I:C), or TSLP. Human fibroblasts and peripheral blood mononuclear cells (PBMCs) were stimulated with the same cytokines. Gene expression (microarray and rt-PCR) and protein levels of phospho-Smad2 were tested.

Results:

TSLP was highly expressed in skin of dcSSc patients, stronger in perivascular areas, where we observed inflammatory cell infiltrates, and in interstitial cells. TSLP expression was co-localized with immune cells, such as CD4+, CD8+, although mainly produced by CD163+ cells. Skin of TSLP-treated mice showed upregulated clusters of genes that overlapped with IL-13 and TGFb-treated mice. In addition, a specific TSLP-cluster showed upregulation of CXCL9, proteasomes, and other interferon-regulated genes. In PBMCs, TSLP alone upregulated mannose-receptor-1 (MRC1), an alternatively-activated macrophage marker, to a similar degree as after IL-13 stimulation. MRC1 was also highly expressed in dcSSc skin compared to controls. TSLP kinetics, along 24 hours of stimulation in PBMCs, showed an early induction of TNF, MX1, and INFg, followed by an induction of CXCL9 and MRC1 gene-expression. Human fibroblasts and skin of mice-treated with TSLP showed TGF-beta-canonical pathway activation with phosphorylation of Smad2. The lack of IL4Ra1 in TSLP-treated mice promotes similar cutaneous inflammation and upregulation of profibrotic markers (PAI-1 and CXCL5). Poly(I:C)-treated mice, a SSc-like murine model, showed high levels of TSLP in similar areas as seen in the skin of dcSSc patients and also mainly in infiltrating immune cells, shown by IHC.  

Conclusion:

TSLP is highly expressed in skin of dcSSc patients, mainly produced by macrophages, and regulates similar genes as other profibrotic cytokines (TGF-beta and IL-13), strongly suggesting that it promotes SSc fibrosis directly or by stimulating production or activation of these cytokines. TSLP also promotes a proinflammmatory effect, which might explain this dual finding in SSc patients.


Disclosure:

R. Christmann,
None;

A. Mathes,
None;

G. Stifano,
None;

A. J. Affandi,
None;

A. Bujor,
None;

C. Padilla,
None;

R. Lafyatis,
None.

  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tslp-upregulation-in-human-ssc-skin-and-induction-of-overlapping-profibrotic-genes-and-intracellular-signaling-with-il-13-and-tgfb/

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.