A Notch signaling antagonist (DAPT) ameliorates autoimmune arthritis in mice by suppressing Th1 and Th17 immune responses.

Authors

Hui Chen, Guangjie Pan, Pingshan Yang, Jun Xie

Published in

Pakistan journal of pharmaceutical sciences. Volume 39. Issue 12. Pages 3825-3834. Dec 01, 2026.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease for which targeted therapies remain limited. The Notch signaling pathway has been implicated in T cell differentiation and autoimmune inflammation.
This study aimed to investigate the therapeutic effects of the Notch signaling antagonist DAPT on autoimmune arthritis in mice and to explore its underlying immunological mechanisms.
A collagen-induced arthritis (CIA) mouse model was established. DAPT (100 ng/kg) or PBS was administered intraperitoneally every other day from day 0 to day 36. Notch pathway activation in CD4+ T cells and synovial tissues was assessed by Western blot and immunohistochemistry. Arthritis severity was evaluated by clinical scoring, radiological examination and histopathology. Th1, Th17 and Treg cell frequencies and absolute numbers in spleen and lymph nodes (LNs) were analyzed by flow cytometry. Plasma cytokine levels were measured by multiplex assay. In-vitro Th17 differentiation assays were performed with DAPT or a Notch agonist.
Compared with normal mice, CIA mice showed significant upregulation of NICD expression in CD4+ T cells and synovial tissues. DAPT treatment significantly reduced clinical arthritis scores, joint erosion and cartilage destruction. DAPT also decreased the frequencies and absolute numbers of Th1 and Th17 cells in the spleen and LNs, alongwith reduced plasma levels of IFN-γ and IL-17. In-vitro, DAPT suppressed Th17 differentiation, while Notch agonist enhanced it. Treg cells were not significantly altered by DAPT.
The Notch signaling antagonist DAPT ameliorates autoimmune arthritis in mice by suppressing Th1 and Th17 immune responses, highlighting Notch signaling as a potential therapeutic target for RA.

PMID:
42708781
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.