AF6 orchestrates macrophage polarization via JAK2-STAT3 signaling and supports intestinal regeneration by stimulating stem cell proliferation.

Authors

Tao Jian, Xiaoxia Dong, Jingwen Kong, Xinyu Wang, Meiyan Qi, Lixing Zhan, Lilei Zhuang

Published in

Frontiers in immunology. Volume 17. Pages 1798313. Epub Jun 19, 2026.

Abstract

Macrophages play a central role in regulating intestinal inflammation, resolution, and tissue repair. However, the upstream regulators that govern their polarization during colitis remain poorly defined.
In this study, we used a dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the scaffold protein AF6 in colitis pathogenesis.
We identify AF6 as a key regulator that promotes pro-inflammatory macrophage polarization and exacerbates colitis. Mechanistically, AF6 expression promoted JAK-STAT3 complex formation. In turn, its deletion in macrophages resulted in impaired JAK-STAT3 signaling pathway and a shift away from pro-inflammatory M1 polarization. Furthermore, the AF6-deficient macrophages were determined to also promote epithelial regeneration through enhanced IL-10 production and downstream activation of Wnt/β-catenin signaling in intestinal organoids culture.
Thus, our study defines a therapeutically amenable AF6-JAK2-STAT3 axis that controls macrophage-driven pathogenesis in colitis, revealing a novel strategy to break the cycle of inflammation and impaired repair.

PMID:
42404906
Bibliographic data and abstract were imported from PubMed on 06 Jul 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.