Dual zeitgeber axes in psoriasis: a chronobiological framework for immune jet lag.

Psoriasis is primarily characterized by interleukin-23/T helper 17 (IL-23/Th17)-related inflammation, but clinical and epidemiological observations also suggest recurrent temporal features, including seasonal fluctuation, nocturnal symptom exacerbation, sleep-wake disturbance, and circadian-related risk contexts. Here, we propose the Dual Zeitgeber Model as a hypothesis-generating and testable chronobiological framework for organizing these observations. The central hypothesis is that persistent misalignment between the light-suprachiasmatic nucleus (SCN)-neuroendocrine axis (Axis I) and the feeding-metabolism-microbiome axis (Axis II) may contribute to immune temporal desynchronization. Within this framework, immune jet lag is reserved for this hypothesized state of immune temporal desynchronization. This concept describes a condition in which neuroendocrine immune gating and metabolic-microbial immune signals may become temporally misaligned. This hypothesis raises several testable questions: whether Axis I-Axis II temporal relationships are associated with disease activity, whether abnormal immune temporal organization persists over time, and whether adjunctive circadian-oriented strategies may provide mechanistic insight or potential clinical value alongside established therapies. More broadly, this framework reframes time as a measurable, stratifiable, and testable research dimension, thereby providing new directions for circadian phenotype-based stratification, longitudinal tracking of disease trajectories and treatment responses, and the design of time-controlled intervention studies.