Immune triad microenvironments define coordinated activation architecture in psoriatic disease.

Psoriatic inflammation reflects contributions from several leukocyte lineages, yet organisational patterns of immune cell cooperation remain largely unexplored. Immune triads, defined as combinations of three lineages within a common spatial microenvironment, represent spatial patterns that may shed light on the inflammatory organisation of psoriasis. Triads formed by dendritic cells (DC), T cells (T) and natural killer cells (NK) integrate antigen presentation and cytotoxic pathways relevant to psoriatic inflammation. Triads that incorporate monocytes, neutrophils and innate-like T cells capture divergent recognition pathways, with γδ T cells providing rapid stress surveillance and mucosal-associated invariant T cells (MAIT) exerting cytokine-driven effector responses. Together these lineage features suggest that these triads may act as immunological contexts that potentially contribute to the architecture of psoriatic inflammation, supporting a systematic assessment of their spatial positioning and activation profiles. This work integrates peripheral CITE-seq profiling with spatial transcriptomics from psoriatic disease to measure systemic activation synchrony, identify triad niches across tissue layers and characterise activation patterns within their spatial microenvironments. The analysis reveals a marked systemic activation synchrony within DC-T-NK triads together with a consistent enrichment of all three triads in psoriatic lesions and a dominant localisation of triad co-occupation within epidermal regions. Within the epidermis, coordinated activation is evident in both DC-T-NK and monocyte-MAIT-neutrophil triads, while severity-linked signals are most prominent in MAIT-containing triads. These findings demonstrate that immune triads provide a unifying framework that connects coordinated activation in tissue with clinically meaningful features of psoriatic inflammation.