ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Maraviroc Attenuates Orbital Remodeling, Inflammation, and Lipid Dysregulation in a Murine Model of Thyroid Eye Disease associated with Graves' Disease
Fahimeh Hashemi Arani 1
Anne Gulbins 1
Mareike Horstmann 1
Insa Nolte 1
Anke Daser 2
Nikolaos E. Bechrakis 1
J Paul Banga 1
Erich Gulbins 3
Anja Katrin Eckstein 1
Gina-Eva Görtz 1
1. Department of Ophthalmology, Molecular Ophthalmology Group, University Hospital Essen, Essen, Germany
2. Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Essen., Essen, Germany
3. Institute of Molecular Biology, University Hospital Essen, Essen, Germany
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Abstract
Background: Graves' disease (GD) is an autoimmune condition that can extend beyond the thyroid, leading to thyroid eye disease (TED), a disorder marked by orbital inflammation and tissue remodeling. Methods: We explored the therapeutic potential of maraviroc, a CCR5 antagonist, in a mouse model of TED triggered by immunization with the human TSH receptor (hTSHR) A-subunit. Mice received pTriEx1.1neo-hTSHR A-subunit plasmid immunizations, and a subset were treated with maraviroc via drinking water. We assessed thyroid function, orbital tissue changes, immune cell infiltration, and lipid metabolism through serological testing, histology, immunohistochemistry, and untargeted lipidomics. Results: Maraviroc did not significantly affect anti-TSHR antibody production nor the degree of hyperthyroidism, though it modestly improved thyroid histopathology. Notably, it reduced key signs of orbital disease, including brown adipose tissue expansion, CCL5-positive immune cell infiltration, CD4+ T-cell infiltration and the presence of F4/80⁺ macrophages. Lipidomic profiling revealed distinct metabolic changes in treated mice, with reduced triacylglycerols and elevated carnitines, indicative of enhanced fatty acid utilization. Composite Z-score analysis reinforced maraviroc's beneficial effects on orbital inflammation and remodeling. Conclusion: Maraviroc shows promise as a targeted therapy for TED in the context of GD, offering anti-inflammatory and anti-adipogenic benefits while sparing thyroid autoimmunity. These preclinical findings support further clinical investigation into its role in managing TED.
Summary
Keywords
CCR5/CCL5, Inflammation, Maraviroc, orbital remodeling, TED
Received
01 October 2025
Accepted
11 February 2026
Copyright
© 2026 Hashemi Arani, Gulbins, Horstmann, Nolte, Daser, Bechrakis, Banga, Gulbins, Eckstein and Görtz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Gina-Eva Görtz
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