Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells

Billi, A. C.; Ma, F.; Plazyo, O.; Gharaee-Kermani, M.; Wasikowski, R.; Hile, G. A.; Xing, X.; Yee, C. M.; Rizvi, S. M.; Maz, M. P.; Wen, F.; Tsoi, L. C.; Pellegrini, M.; Modlin, R. L.; Gudjonsson, J. E.; Kahlenberg, J. M.

doi:10.1101/2021.09.17.460124

bioRxiv · 10.1101/2021.09.17.460124

Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells

Billi, A. C.·Ma, F.·Plazyo, O.·Gharaee-Kermani, M.·Wasikowski, R.·Hile, G. A.·Xing, X.·Yee, C. M.·Rizvi, S. M.·Maz, M. P.·Wen, F.·Tsoi, L. C.·Pellegrini, M.·Modlin, R. L.·Gudjonsson, J. E.·Kahlenberg, J. M.

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Abstract

Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Studies to date suggest that non-lesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA-sequencing and spatial-seq. We demonstrate that normal-appearing skin of lupus patients represents a type I interferon-rich, prelesional environment that skews gene transcription in all major skin cell types and dramatically distorts cell-cell communication. Further, we show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining pro-inflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and non-lesional skin in lupus and identify a role for skin education of CD16+ dendritic cells in CLE pathogenesis.

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Billi, A. C., Ma, F., Plazyo, O., Gharaee-Kermani, M., Wasikowski, R., Hile, G. A., Xing, X., Yee, C. M., Rizvi, S. M., Maz, M. P., Wen, F., Tsoi, L. C., Pellegrini, M., Modlin, R. L., Gudjonsson, J. E., Kahlenberg, J. M.. 2021-09-20. Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells. https://doi.org/10.1101/2021.09.17.460124

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