ArticleImmunity, inflammation and disease2023
AhR agonist tapinarof ameliorates lupus autoimmunity by suppressing Tfh cell differentiation via regulation of the JAK2-STAT3 signaling pathway.
Article in Immunity, inflammation and disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 11 citations in OpenAlex.
- [Role of AHR-mediated histone acetylation at FOXP3 in Tfr cell differentiation in systemic lupus erythematosus].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- The Therapeutic Effect of Tapinarof on In Vitro Cutaneous Lupus-like Keratinocyte Model.International journal of molecular sciences · 2026Article
- Aryl hydrocarbon receptor-mediated transcriptional regulation of HSP70 exacerbates endoplasmic reticulum stress in lupus nephritis.Cell & bioscience · 2026Article
- Gut metabolite indole-3-acetic acid aggravates neuropsychiatric lupus via the AHR/STAT3 pathway in microglia.Communications biology · 2026Article
- Targeting STAT3 in systemic lupus erythematosus and lupus nephritis: mechanisms, therapeutic advances, and structure-informed perspectives.Frontiers in pharmacology · 2026Review
- AhR agonist Ficz modulates T follicular helper cells and ameliorates skin fibrosis in a bleomycin-induced SSc mouse model.Journal of scleroderma and related disorders · 2026Article
- Aryl Hydrocarbon Receptor in Health and Disease.MedComm · 2025Review
- Disproportionality analyses of Tapinarof-related adverse events based on the FAERS database.Archives of dermatological research · 2025Article
- The AhR pathway is dysregulated in alopecia areata.Journal of translational autoimmunity · 2025Article
- AhR regulation of amyloid beta-induced inflammation in astrocyte cells.Frontiers in cellular neuroscience · 2025Article
- Successful treatment of discoid lupus erythematosus with tapinarof 1% cream monotherapy.JAAD case reports · 2024Article
- AhR agonist tapinarof ameliorates lupus autoimmunity by suppressing Tfh cell differentiation via regulation of the JAK2-STAT3 signaling pathway.Immunity, inflammation and disease · 2023Article
- Th1-related transcription factors and cytokines in systemic lupus erythematosus.Frontiers in immunology · 2023Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aryl hydrocarbon receptor (AhR) is a critical regulator of the pathogenesis of autoimmune disorders. We aimed to investigate the therapeutic effect of the AhR agonist tapinarof during the development of systemic lupus erythematosus (SLE).
methodsMRL/lpr mice were intraperitoneally injected with 1 or 5 mg/kg tapinarof for 6 weeks. Kidney histopathology was evaluated using hematoxylin and eosin (H&E) and Periodic-Acid-Schiff (PAS) staining. Immunofluorescence microscopy was performed to detect immune complex renal depositions. Flow cytometry (FCM) analysis was carried out to determine the proportions of T and B cell subsets. Realtime qPCR was used to quantify the expression of Tfh cell-associated genes. We conducted an in vitro polarization experiment to observe the effect of tapinarof on Tfh differentiation. Western blotting was used to detect the expression of target proteins.
resultsWe found that tapinarof treatment ameliorated lupus phenotypes, including splenomegaly, lymph node enlargement, kidney damages, immune complex deposition, and excessive secretion of antibodies. Additionally, we showed that Treg subpopulation frequencies significantly increased in MRL/lpr mice treated with tapinarof, while the proportion of Th1/Th2 cells was reduced after tapinarof administration. Moreover, tapinarof suppressed Tfh cell differentiation and germinal center (GC) reaction in vivo. The inhibitory effect of tapinarof on Tfh cells was further verified in the in vitro Tfh cell polarization experiment. Realtime qPCR revealed that tapinarof repressed the expression of Tfh signature genes. Mechanistically, tapinarof significantly inhibited the phosphorylation levels of JAK2 and STAT3. The capacity for Tfh differentiation was partially rescued by the STAT3 activator Colivelin TFA. Furthermore, our in vitro Tfh polarization experiments indicated that tapinarof suppressed Tfh cell development in SLE.
conclusionsOur data demonstrated that tapinarof modulated the JAK2-STAT3 pathway to suppress Tfh cell differentiation for the treatment of lupus symptoms in MRL/lpr mice.
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