Interleukin-27 is a multitarget regulator of fibroblast remodeling in thyroid-associated ophthalmopathy

  • iScience. 2025 Nov 10;28(12):113982. doi: 10.1016/j.isci.2025.113982.
Pengbo Zhang  1  2 ,  Xiaofang Wang  3 ,  Nanji Lu  1  2 ,  Yan Nie  1  2 ,  Xibo Zhang  4 ,  Longqian Liu  1  2
Affiliations
  • 1. Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
  • 2. Laboratory of Optometry and Vision Sciences, West China Hospital, Sichuan University, Chengdu, China.
  • 3. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 4. Department of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
PMID: 41362621 DOI: 10.1016/j.isci.2025.113982
Abstract

Thyroid-associated ophthalmopathy (TAO) is characterized by inflammation and tissue remodeling, including fibrosis and adipogenesis. Here, we identify interleukin-27 (IL-27) as a negative feedback immunomodulator in TAO. Serum IL-27α levels were significantly elevated in patients with TAO compared with healthy and inflammatory disease controls. In orbital fibroblasts (OFs), exogenous IL-27 suppressed IL-1β-induced proinflammatory cytokines and reduced hypoxia-induced NLRP3 inflammasome activation. IL-27 also attenuated TGF-β-driven fibrosis via p38 MAPK signaling in CD90+ OFs. Furthermore, in CD90- OFs, IL-27 restrained adipogenic differentiation by dampening Akt signaling and suppressing hypoxia-induced adipogenesis in a ROS-dependent manner. Our results indicate that IL-27 signaling acts as a multifunctional regulator and negative feedback modulator that helps limit the pathological progression of TAO.

Keywords
Ophthalmology; fibrosis; immune response.
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