Platelet-Immune-Neuron Crosstalk Modulates Cutaneous Inflammation and Pruritus

Methods

Optogenetic platelet activation, platelet depletion, serotonin depletion and TRPV1+ neuron specific deletion of HTR2B were used to determine the functional relevance of platelets in cutaneous inflammation and itch. Results: Upon optogenetic stimulation, activated platelets were attracted to the inflamed lesion, which elicits erythema, edema and pruritus in mice. Then a characteristic transcriptomics of photostimulated lesion showed a pathogenetic resemblance to skin disorders, especially atopic dermatitis (AD).

Platelet depletion alleviated scratching behaviors and skin pathology in AD, whereas platelet activation exacerbated both. Subsequently, depletion of serotonin (5-HT) released from platelets reduced the spontaneous scratching and cutaneous inflammation by C-fiber excitability and suppressing macrophage infiltration. For itch transmission, genetic approaches reveal that platelet-derived serotonin activates TRPV1⁺ pruriceptors through HTR2B receptors in AD.

Conclusions: These data showed the sufficiency of platelet activation for cutaneous inflammation and itch, which uncovered a novel platelet-immune-neuron axis as a promising therapeutic target for AD and potentially other skin disorders.