Immunological liver-skin axis: a systemic Vγ4+ γδT17 cell responselinks psoriasis-like inflammation and MASLD

Fleissner, J.; Rocca, Y.; Freund, L.; Ossner, T.; Imdahl, F.; Doucet Ladeveze, R.; Kurz, F.; Geier, A.; Goebeler, M.; Gasteiger, G.; Kerstan, A.

doi:10.64898/2025.12.22.695890

bioRxiv · 10.64898/2025.12.22.695890

Immunological liver-skin axis: a systemic Vγ4+ γδT17 cell responselinks psoriasis-like inflammation and MASLD

Fleissner, J.·Rocca, Y.·Freund, L.·Ossner, T.·Imdahl, F.·Doucet Ladeveze, R.·Kurz, F.·Geier, A.·Goebeler, M.·Gasteiger, G.·Kerstan, A.

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and psoriasis frequently co-occur and share interleukin-17 (IL-17)-mediated inflammatory mechanisms. Using a murine model combining Western-diet-induced early MASLD with chronic imiquimod-triggered psoriasis-like dermatitis, we observed exacerbated skin inflammation with increased cellularity and systemic IL-17-driven immune activation. In mice with psoriasis-like skin inflammation, hepatic {gamma}{delta}T cells shifted from IFN-{gamma}-producing {gamma}{delta}T1 toward IL-17-secreting {gamma}{delta}T17 cells, accompanied by an acute-phase response and induction of hepatic lipogenic gene expression. Single-cell RNA sequencing revealed an expansion of V{gamma}4 {gamma}{delta}T17 cells engaged in IL-17 and TGF-{beta} signaling, consistent with early fibrogenic responses. Together, these findings identify V{gamma}4 {gamma}{delta}T17 cells as a mechanistic link between psoriasis and MASLD, promoting systemic inflammation and early hepatic remodeling. Consistently, in a clinical cohort of patients with moderate-to-severe psoriasis and co-morbid MASLD, IL-17-targeted therapy improved hepatic steatosis, underscoring the translational relevance of this immunological axis.

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Fleissner, J., Rocca, Y., Freund, L., Ossner, T., Imdahl, F., Doucet Ladeveze, R., Kurz, F., Geier, A., Goebeler, M., Gasteiger, G., Kerstan, A.. 2025-12-23. Immunological liver-skin axis: a systemic Vγ4+ γδT17 cell responselinks psoriasis-like inflammation and MASLD. https://doi.org/10.64898/2025.12.22.695890

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