Single-cell transcriptomics suggest distinct upstream drivers of IL-17A/F in hidradenitis versus psoriasis - 08/09/23
, Jongmi Lee, MD, PhD b, Xuan Li, BS c, Hyun Soo Lee, MD c, Katherine Kim b, Vasuma Chaparala b, William Murphy, PhD a, Wei Zhou, PhD d, Junyue Cao, PhD d, Michelle A. Lowes, MBBS, PhD c, James G. Krueger, MD, PhD c, ⁎ 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 numéro
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