FGF21 induced by endoplasmic reticulum stress maintains medullary thymic epithelial cell function and central immune tolerance.

Authors

Yuki Masuda, Yoshiaki Nakayama, Ryohei Shimizu, Hiroshi Hasegawa, Morichika Konishi

Published in

Science advances. Volume 12. Issue 29. Pages eaee9999. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Medullary thymic epithelial cells (mTECs) establish central immune tolerance by expressing diverse tissue-restricted antigens and eliminating self-reactive thymocytes. Here, we show that fibroblast growth factor 21 (FGF21), although predominantly produced in the liver, is also expressed locally by mature mTECs and contributes to central tolerance. Fgf21-deficient mice exhibited exacerbated peripheral autoimmune responses. FGF21 supported the number and function of mTECs and promoted clonal deletion in cooperation with thymic dendritic cells. In mature mTECs, endoplasmic reticulum stress induced FGF21 expression through unfolded protein response pathways, with FGF21 acting preferentially within the mature mTEC compartment as a stress-responsive metabolic regulator downstream of the integrated stress response. By limiting sustained stress and preserving protein homeostasis, FGF21 maintained mTEC integrity and central tolerance. These findings identify FGF21 as a key regulator of thymic immune homeostasis and as a potential therapeutic target for autoimmune disease.

PMID:
42467778
Bibliographic data and abstract were imported from PubMed on 18 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.