Single-cell transcriptomic landscape of immunometabolism reveals intervention candidates of ascorbate and aldarate metabolism, fatty-acid degradation and PUFA metabolism of T-cell subsets in healthy controls, psoriasis and psoriatic arthritis

Lu Peng; Ling Chen; Jianji Wan; Wenqi Liu; Shuang Lou; Zhu Shen

doi:10.3389/fimmu.2023.1179877

Single-cell transcriptomic landscape of immunometabolism reveals intervention candidates of ascorbate and aldarate metabolism, fatty-acid degradation and PUFA metabolism of T-cell subsets in healthy controls, psoriasis and psoriatic arthritis

Front Immunol. 2023 Jul 10:14:1179877. doi: 10.3389/fimmu.2023.1179877. eCollection 2023.

Authors

Lu Peng¹, Ling Chen², Jianji Wan¹, Wenqi Liu¹, Shuang Lou¹, Zhu Shen¹

Affiliations

¹ Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
² Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, China.

Abstract

Introduction: The modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic disease and the potential targets for immunometabolic intervention in the different T-cell subsets involved in its pathogenesis remain unclear.

Methods: In this study, we analyzed circulating blood single-cell data from healthy controls (HC), psoriasis (PSO), and psoriatic arthritis (PSA) patients, and revealed their metabolic features of T-cell subsets: CD4+ central memory T cells (TCMs), CD8+ effective memory T cells (TEMs), regulatory T cells (Tregs), mucosal-associated invariant T cells (MAITs ), and γδ T cells. Pearson test was performed to determine the linkages between differential metabolic and inflammatory pathways. Based on these results, we also analyzed the potential impacts of biological antibodies on differential metabolic pathways by comparing the immunometabolism differences between PSA patients without and with biological treatment.

Results: Our results suggest that upregulation of ascorbate and aldarate metabolism, as well as fatty acid degradation, may enhance the immune suppression of Tregs. Enhanced metabolism of alpha-linolenic acid, linoleic acid, and arachidonic acid may inhibit the pro-inflammatory functions of CD4+ TCMs and CD8+ TEMs in PSO and PSA, and protect the immune suppression of Tregs in PSA. We propose that supporting ascorbic acid and fatty acid metabolic pathways may be an adjunctive reprogramming strategy with adalimumab and etanercept therapy.

Discussion: These findings not only provide insights into immunometabolism characteristics of psoriatic disease, but also offer preliminary options for the auxiliary treatment of psoriasis.

Keywords: TCM; TEM; Treg; immunometabolism; psoriasis; psoriatic arthritis; single-cell transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Psoriatic*
Ascorbic Acid / therapeutic use
Humans
Psoriasis*
T-Lymphocyte Subsets / metabolism
Transcriptome

Substances

Ascorbic Acid

Grants and funding

National Natural Science Foundation of China (No. 82273537, 82073444); The supporting scientific fund for talent introduction of Guangdong Provincial People’s Hospital (KJ0120220181).