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In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (\u22122.3 points, SD 1.1, p=0.002) and Skindex-16 (\u221221.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.<\/jats:p>","DOI":"10.64898\/2026.03.13.26348272","type":"posted-content","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:40:11Z","timestamp":1774226411000},"source":"Crossref","is-referenced-by-count":1,"title":["TYK2 Inhibition with Deucravacitinib Improves Clinical Outcomes and Resolves Interferon-Driven Inflammation in Lichen Planopilaris"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6900-2615","authenticated-orcid":false,"given":"Alyssa","family":"Stockard","sequence":"first","affiliation":[{"name":"Mayo Clinic Arizona Department of Dermatology, Scottsdale, Arizona, 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