{
  "abstract": "T helper 17 (Th17) cells and their key effector cytokine, particularly IL-17A and IL-17F, play central roles in host defense against extracellular pathogens. However, they are also critically involved in the pathogenesis of many autoimmune and inflammatory diseases. Th17 cell differentiation, stabilization, plasticity, and pathogenicity are regulated by a network of cytokines and transcription factors, including IL-6, TGF-β, IL-23, STAT3, and the key transcription factor RORγt. RORγt-dependent pathways are also relevant to other immune populations, including group 3 innate lymphoid cells (ILC3s), highlighting the complexity of the IL-17 axis across tissues. Dysregulation of these pathways can lead to chronic inflammation and tissue damage in diseases such as psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Therapeutic targeting of the Th17 axis has led to clinically established approaches, particularly direct blockade of IL-17 signaling and inhibition of IL-23, whereas direct RORγt inhibition remains an investigational strategy. RORγt inhibitors may modulate Th17 differentiation and broader RORγt-dependent transcriptional programs, but their clinical development has been challenged by variable efficacy, safety considerations, and translational limitations. This review provides a comprehensive overview of Th17 biology, focusing on differentiation, plasticity, tissue-specific functions, and the contribution of Th17 and other RORγt-expression populations to autoimmune diseases. Furthermore, it critically compares established IL-17-targeted therapies with emerging RORγt inhibitors, emphasizing their distinct mechanisms, cellular and molecular targets, clinical evidence, safety, and developmental status. Finally, we discuss combination strategies, translational challenges, and emerging biomarkers that may contribute to more individualized therapeutic approaches and patient stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Intelligent Automation and BioMed Genomics Laboratory (IABL), Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University",
    "Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Science, College of Health Sciences, Bayero University",
    "Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University",
    "Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia",
    "Department of Medical Biochemistry, Faculty of Medicine, Selcuk University",
    "Jefferson Headache Center, Department of Neurology, Thomas Jefferson University",
    "LR21ES03 Research Laboratory “Oncogenesis and Tumor Progression”, Faculty of Medicine of Sousse, University of Sousse",
    "Department of Medical Laboratory Science, College of Medical Sciences, Ahmadu Bello University",
    "The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center",
    "Non-communicable Diseases Research Center, Alborz University of Medical Sciences",
    "Department of Neurology, Thomas Jefferson University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zeineb Zian"
    },
    {
      "affs": [
        1
      ],
      "name": "Mansur Aliyu"
    },
    {
      "affs": [
        2
      ],
      "name": "Fariha Hossain"
    },
    {
      "affs": [
        3
      ],
      "name": "Fatema Tuz Zohora"
    },
    {
      "affs": [
        4
      ],
      "name": "Ayça Ceylan"
    },
    {
      "affs": [
        0
      ],
      "name": "Nada Ben Moussa"
    },
    {
      "affs": [
        5
      ],
      "name": "Wan-Jen Hsieh"
    },
    {
      "affs": [
        6
      ],
      "name": "Feirouz Abbes"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Sharafudeen D. Abubakar"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Gholamreza Azizi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/50yd1whqpygp2.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1941866",
  "fulltext_url": null,
  "id": "50yd1whqpygp2",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941866/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Psoriasis: Treatment and Pathogenesis"
    ]
  ],
  "openalex": "W7223854323",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1941866/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/50yd1whqpygp2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1941866",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941866/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Psoriasis: Treatment and Pathogenesis",
      "subfield": "immunology"
    }
  ],
  "title": "Th17 suppression strategies: targeting IL-17 and RORγt pathways in autoimmune diseases",
  "title_text": "Th17 suppression strategies: targeting IL-17 and RORγt pathways in autoimmune diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/50yd1whqpygp2",
  "venue": "Frontiers in Immunology",
  "versions": []
}