Single-cell transcriptomics suggest distinct upstream drivers of IL-17A/F in hidradenitis versus psoriasis - 08/09/23
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Abstract |
Background |
On the basis of the mounting evidence that type 17 T (T17) cells and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologic agents used previously in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS.
Objective |
Our research aimed to characterize the transcriptome of HS T17 cells compared to the transcriptome of psoriasis T17 cells, along with their ligand–receptor interactions with neighborhood immune cell subsets.
Methods |
Single-cell data of 12,300 cutaneous immune cells from 8 deroofing surgical HS skin samples including dermal tunnels were compared to single-cell data of psoriasis skin (19,525 cells from 11 samples) and control skin (11,920 cells from 10 samples). All single-cell data were generated by the same protocol.
Results |
HS T17 cells expressed lower levels of IL23R and higher levels of IL1R1 and IL17F compared to psoriasis T17 cells (P < .05). HS Treg cells expressed higher levels of IL1R1 and IL17F compared to psoriasis Treg cells (P < .05). Semimature dendritic cells were the major immune cell subsets expressing IL1B in HS, and IL-1β ligand–receptor interactions between semimature dendritic cells and T17 cells were increased in HS compared to psoriasis (P < .05). HS dermal tunnel keratinocytes expressed inflammatory cytokines (IL17C, IL1A, IL1B, and IL6) that differed from the HS epidermis keratinocytes (IL36G) (P < .05). IL6, which synergizes with IL1B to maintain cytokine expression in T17 cells, was mainly expressed by fibroblasts in HS, which also expressed IL11+ inflammatory fibroblast genes (IL11, IL24, IL6, and POSTN) involved in the paracrine IL-1/IL-6 loop.
Conclusion |
The IL-1β–T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-1β signaling, unlike psoriasis T17 cells, which are activated by IL-23 signaling.
Le texte complet de cet article est disponible en PDF.Key words : Hidradenitis suppurativa, psoriasis, IL-17A, IL-17F, IL-23, IL-1, IL-1R1, type 17 T cells, single-cell RNA sequencing, T cell, dendritic cell, keratinocyte, fibroblast
Abbreviations used : DC, FC, HS, KC, T17, Treg
Plan
Vol 152 - N° 3
P. 656-666 - septembre 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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