Single-cell Characterisation of Inflammatory Signatures in Psoriasis and Systemic Lupus Erythematosus

Abstract

Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and psoriasis are characterised by dysregulated immune responses. Chronic inflammation is often present in these diseases. Characterization of inflam- matory signatures, shared autoimmune signatures, and disease-specific signa- tures at the cell type level might help improving diagnostics and therapeutic approaches. We developed a bioinformatic workflow and used it to anal- yse publicly available scRNAseq datasets from blood and skin samples for psoriasis and SLE. After the cell type annotation and differential expression analysis we were able to reveal inflammatory and shared autoimmune signa- tures in several cell types in skin. In particular, we identified inflammatory signatures in keratinocytes in both diseases. Our results further suggest that monocytes, fibroblasts, and T cells are the key players in skin inflammation in SLE. Finally, we characterized signatures that are shared between the two diseases in individual skin cell types. Importantly, we observed IFN signaling signature in keratinocytes and monocytes.

Syste ́mova ́ autoimunitnı ́ onemocne ̌nı ́, jako syste ́movy ́ lupus erythema- todes (SLE) a psoria ́za, jsou charakterizova ́na dysregulovanou imunitnı ́ od- pove ̌dı ́, s c ̌astou pr ̌ı ́tomnostı ́ chronicke ́ho za ́ne ̌tu. Charakterizace za ́ne ̌tlivy ́ch signatur, sdı ́leny ́ch autoimunitnı ́ch signatur a signatur specificky ́ch pro jed- notlive ́ nemoci na u ́rovni bune ̌c ̌ny ́ch typu ̊ mu ̊z ̌e pomoci zleps ̌it diagnostiku a le ́c ̌ebne ́ postupy. V te ́to pra ́ci jsme vyvinuli bioinformaticky ́ postup analy ́zy a vyuz ̌ili jej k analy ́ze ver ̌ejne ̌ dostupny ́ch scRNAseq datasetu ̊ z krevnı ́ch a koz ̌nı ́ch vzorku ̊ psoria ́zy a SLE. Po anotaci bune ̌c ̌ny ́ch typu ̊ a analy ́ze di- ferencia ́lnı ́ exprese jsme objevili za ́ne ̌tlive ́ a sdı ́lene ́ autoimunitnı ́ signatury v ne ̌kolika bune ̌c ̌ny ́ch typech v ku ̊z ̌i. Zejme ́na jsme identifikovali za ́ne ̌tlive ́ signatury v keratinocytech v obou nemocech. Nas ̌e vy 'sledky da ́le naznac ̌ujı ́, z ̌e monocyty, fibroblasty a T lymfocyty jsou klı ́c ̌ovy ́mi hra ́c ̌i v za ́ne ̌tu v ku ̊z ̌i v SLE. Da ́le jsme charakterizovali signatury, ktere ́ jsou sdı ́lene ́ mezi zkou- many ́mi nemocemi v jednotlivy ́ch koz ̌nı ́ch bune ̌c ̌ny ́ch typech. Pr ̌edevs ̌ı ́m jsme zachytili IFN signa ́lnı ́ signaturu v keratinocytech a monocytech.