Time of day-dependent immune dynamics are associated with disease severity and therapeutic response in psoriasis

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with substantial patient burden. Symptoms often worsen later in the day, suggesting time-of-day (ToD)-dependent variation, although the underlying systemic immune correlates remain poorly understood. OBJECTIVE: To investigate ToD-dependent variation in immune parameters and inflammatory mediators in psoriasis and their associations with disease severity and treatment response. METHODS: Peripheral blood samples were collected in the morning and evening before and after anti-IL-23 therapy. Immune cell subsets, serum cytokines, and chemokines were quantified. Public skin transcriptomic datasets were analysed using the ZeitZeiger algorithm to infer sampling time and assess ToD-dependent inflammatory signatures. RESULTS: Patients with psoriasis exhibited attenuated time-of-day variation in circulating lymphocytes, largely driven by reduced evening lymphocyte counts. In parallel, patients showed an evening-biased inflammatory profile characterized by increased cytokines and chemokines involved in inflammation and leukocyte migration. Anti-IL-23 therapy reduced inflammatory mediator levels and partially restored disrupted diurnal immune dynamics, particularly at the evening time point. The extent of diurnal variation was associated with disease severity: ToD-dependent variation in IL-31 positively correlated with PASI, whereas variation in Th17 cells and the CD4+/CD8+ ratio showed negative correlations. Non-responders exhibited higher pre-treatment evening IL-31 levels and a more pro-inflammatory immune profile. Consistently, transcriptomic analyses revealed enhanced late-ToD inflammatory activity and immune cell infiltration in lesional psoriatic skin, both of which were attenuated after treatment. CONCLUSION: Psoriasis is characterized by altered time-of-day-dependent immune dynamics, including reduced ToD variation in circulating lymphocytes and a late-ToD pro-inflammatory profile. These findings suggest that temporal immune dysregulation is associated with disease activity and treatment response, and that anti-IL-23 therapy may partially restore disrupted time-of-day immune variation. Consideration of temporal immune context may improve biomarker interpretation and help inform future therapeutic strategies.