Voclosporin shows protective effect and intestinal barrier enforcement in experimental colitis

TL;DR

Voclosporin, a drug approved for lupus nephritis, shows promise in treating intestinal inflammation by strengthening the intestinal barrier in a mouse model of colitis.

Contribution

This study demonstrates that Voclosporin is more effective than cyclosporine A in protecting the intestinal barrier and reducing inflammation in experimental colitis.

Findings

Voclosporin treatment increases barrier-strengthening claudin 3 in the colon of mice with colitis.

Both Voclosporin and cyclosporine A reduce intestinal inflammation and weight loss in experimental colitis models.

Voclosporin inhibits the activation of ITK, a key driver of inflammation in inflammatory bowel disease.

Abstract

The treatment of inflammatory bowel disease (IBD) is still challenging. Therefore, it is crucial not only to develop new drugs specifically targeting IBD but also to evaluate the application and efficacy of already established pharmaceuticals used for related disorders. A promising new candidate is Voclosporin (Voc), a recently approved drug for lupus nephritis. In this study, we aimed to further elucidate the efficiency and the molecular mechanism of action of Voclosporin in comparison with its analogon cyclosporine A (CsA). Using an experimental colitis model and human PBMCs, we performed a comprehensive analysis including mini-endoscopy, histopathology, multi-photon endomicroscopy (MPEM), immunofluorescence staining, flow cytometry, and cytokine secretion profiling of murine lamina propria mononuclear cells (LPMCs). Treatment with Voc or CsA improved colitis-associated weight loss and reduced intestinal inflammation as assessed by endoscopy and histopathological stainings. Treatment with Voclosporin led to a significant increase of the barrier-strengthening protein claudin 3 in the colon of mice with experimentally induced colitis. Furthermore, treatment of stimulated human-derived PBMCs from healthy controls with Voclosporin and CsA inhibited the activation of IL2-inducible tyrosine kinase ITK, a known trigger of inflammation in IBD. These results further support the potential of Voclosporin as a promising therapeutic strategy for the treatment of acute intestinal inflammation.

Voclosporin and CsA have a protective effect and strengthen the intestinal barrier in experimental colitis, with Voclosporin having a more pronounced effect. Treatment with CsA or Voclosporin reduces inflammation in the intestine. At the molecular level, treatment with calcineurin inhibitors leads to an increase in claudin 3, which helps to restore the intestinal barrier, while the amount of pore-forming claudin 2 remains unchanged. Created in BioRender. Knauß, A. (2026) https://BioRender.com/l1hkpqy.Diagram illustrating the effect of CsA/Voc treatment on inflammation in a mouse model. The left panel shows inflammation with increased Claudin-2. The right panel, post-treatment, shows Claudin-3 predominance. The lower images compare inflamed versus treated intestinal sections, highlighting reduced inflammation after treatment.

Voclosporin and CsA have a protective effect and strengthen the intestinal barrier in experimental colitis, with Voclosporin having a more pronounced effect. Treatment with CsA or Voclosporin reduces inflammation in the intestine. At the molecular level, treatment with calcineurin inhibitors leads to an increase in claudin 3, which helps to restore the intestinal barrier, while the amount of pore-forming claudin 2 remains unchanged. Created in BioRender. Knauß, A. (2026) https://BioRender.com/l1hkpqy.

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