Single-cell transcriptomics suggest distinct upstream drivers of IL-17A/F in hidradenitis versus psoriasis

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 IL17A 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-1 beta 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-1 beta-T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-113 signaling, unlike psoriasis T17 cells, which are activated by IL -23 signaling.

Automated summary

This study characterized the transcriptome of HS T17 cells compared to psoriasis T17 cells and investigated their interactions with immune cell subsets. The results indicate that IL-1 beta-T17 cell cytokine axis is likely a dominant pathway in HS, and the interaction between semimature dendritic cells and T17 cells is increased in HS compared to psoriasis.