Spatial Imbalance of Innate-like T-Cell Niches Underlies Clinical Trajectories in Psoriasis

Innate-like T cells (iLTCs) are rapid sentinels at epithelial surfaces, yet their spatial organisation and tissue-linked programmes in psoriatic inflammation remain incompletely defined. Spatial transcriptomics from independent cohorts maps γδT and mucosal-associated invariant T cells (MAIT) niches across psoriatic skin and reveals sharply divergent skin-layer arrangements. Psoriatic plaques show expansion of both niches, with γδT transcriptional signatures present in dermis and epidermis and MAIT signatures strongly enriched in the epidermis. Their compartment-specific positioning is mirrored by distinct transcriptional activities that support dermal-sentinel behaviour for γδT-enriched niches and epithelial-retention programmes for MAIT niches. Clinical severity associates with opposite niche dynamics, marked by decreasing dermal γδT frequencies and increasing epidermal MAIT abundance. Functional profiles reinforce this divergence, as dermal γδT niches display rising exhaustion-associated features with greater severity, whereas epidermal MAIT niches show stronger inflammatory and proliferation-related signals. Peripheral CITE-seq profiling identifies parallel systemic patterns, with reduced γδT frequencies and increased MAIT frequencies in blood, along with exhaustion-associated features in γδT cells and MAIT-specific trafficking cues that align with their behaviour in psoriatic tissue. Together the findings define a spatially imbalanced γδT-MAIT axis in psoriatic inflammation that is linked to layer-specific organisation to local inflammatory cues, systemic immune engagement and clinical severity.