Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome

Cavagnero, K. J.; Albright, J.; Li, F.; Dokoshi, T.; Bogle, R.; Kirma, J.; Kahlenberg, J. M.; Billi, A. C.; Fox, J.; Coon, A.; Dobry, C. J.; Hinds, B.; Tsoi, L. C.; Harms, P. W.; Gudjonsson, J. E.; Gallo, R. L.

doi:10.1101/2024.06.24.600500

bioRxiv · 10.1101/2024.06.24.600500

Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome

Cavagnero, K. J.·Albright, J.·Li, F.·Dokoshi, T.·Bogle, R.·Kirma, J.·Kahlenberg, J. M.·Billi, A. C.·Fox, J.·Coon, A.·Dobry, C. J.·Hinds, B.·Tsoi, L. C.·Harms, P. W.·Gudjonsson, J. E.·Gallo, R. L.

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Abstract

Sweets syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweets syndrome revealed a prominent interferon signature in Sweets syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweets syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweets syndrome through recognition of type I interferons.

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Cavagnero, K. J., Albright, J., Li, F., Dokoshi, T., Bogle, R., Kirma, J., Kahlenberg, J. M., Billi, A. C., Fox, J., Coon, A., Dobry, C. J., Hinds, B., Tsoi, L. C., Harms, P. W., Gudjonsson, J. E., Gallo, R. L.. 2024-06-28. Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome. https://doi.org/10.1101/2024.06.24.600500

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