110 Papillary fibroblasts expressing tenascin-C define a stromal niche that facilitates neuro-immune synapse formation and promotes skin inflammation

Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during inflammation have not been characterized. Here we identified an inflammation-induced subset of papillary that promoted aberrant neurite outgrowth psoriasiform by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis fibroblast lineages revealed aTnc+papillary with pro-axonogenesis neuro-regulation transcriptomic hallmarks. TNC overexpression boosted co-cultured neurons, fibroblast-specific ablation suppressed hyperinnervation, immune cell infiltration, alleviated a psoriasis mouse model. γδT cells, main producers type 17 pathogenic cytokines, frequently contacted nerve fibers lesions were likely modulated postsynaptic signals. Overall, our results highlight role inflammation-responsive facilitating neuro-immune synapse formation suggest potential avenues for future therapeutic research.