Dataset Information

Effect of fatty acid synthesis inhibition in IL-17-producing gamma delta T (γδT17) cells upon psoriatic inflammation

ABSTRACT: γδ T cells represent the primary innate source of IL-17 (γδT17) and are known to play a critical role in autoimmune and inflammatory diseases such as psoriasis. We here reported that psoriatic condition (IL-1b and IL-23) reshaped γδT17 cell metabolic signatures and promoted cytokine expression levels compared to homeostatic condition (IL-7). Acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme of fatty acid synthesis (FAS), directs the fate of IL-17-producing CD4 T cells (Th17) differentiation. However, little is known about the role of ACC1-mediated FAS in their innate IL-17-producer counterpart, γδT17 cells. We further investigated the role of FAS in γδT17 by comparing the effect of pharmacological inhibitor Soraphen A (SorA) on DMSO vehicle under psoriatic conditions (IL-1b and IL-23). Interestingly, ACC inhibition shifts the lipid metabolism in γδT17 cells, which allows them to cope with lipid demand without affecting cellular viability.

ORGANISM(S): Mus musculus

PROVIDER: GSE256512 | GEO | 2025/02/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Based on the mounting evidence that Type 17 T-cells (T17 cells) and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologics previously used in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS. Objective: Our aim was to characterize the transcriptome of HS T17 cells compared to the transcriptome of psoriasis T17 cells, and their ligand-receptor interactions with neighborhood immune cell subsets. Methods: Single-cell data of 12,300 cutaneous immune cells from 8 de-roofing surgical HS skin samples that included dermal tunnels were compared with single-cell data of psoriasis skin (19,525 cells from 11 samples) and control skin (11,920 cells from 10 samples). All the single-cell data were generated by the identical protocol. Results: HS T17 cells expressed lower levels of IL23R and higher levels of IL1R1 and IL17F compared to psoriasis T17 cells (p < 0.05). HS regulatory T-cells (Tregs) expressed higher levels of IL1R1 and IL17F compared to psoriasis Tregs (p < 0.05). Semimature dendritic cells (DCs) were the major immune cell subsets expressing IL1B in HS, and IL-1B ligand-receptor interactions between semimature DCs and T17 cells were increased in HS compared to psoriasis (p < 0.05). HS dermal tunnel keratinocytes (KCs) expressed inflammatory cytokines (IL17C, IL1A, IL1B, and IL6) different from HS epidermis KCs (IL36G) (p < 0.05). 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 paracrine IL-1/IL-6 loop. Conclusion: The IL-1B-T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-1B signaling, unlike psoriasis T17 cells which are activated by IL-23 signaling. Clinical Implication: Biologics targeting IL-17 isoforms and IL-1B may be effective for HS but biologics targeting IL-23 may be less effective for HS.

Dataset Information

Effect of fatty acid synthesis inhibition in IL-17-producing gamma delta T (γδT17) cells upon psoriatic inflammation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets