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Single-cell immune ecosystem and metabolism reprogramming imprinted by psoriasis niche
Boxuan Jiang1,2, Han Zhang1,2, Yingcheng Wu3
1Department of Dermatology, Third Affiliated Hospital of Nantong University, Nantong Third People's Hospital, Nantong, China.
Annals of Translational Medicine
|August 29, 2022
Summary
Psoriasis involves a dysfunctional immune environment. This study reveals unique immune cell profiles and metabolic abnormalities in T cells, offering new therapeutic targets for this skin disease.
Area of Science:
- Immunology
- Dermatology
- Systems Biology
Background:
- Psoriasis is characterized by a dysfunctional immune niche, with limited understanding of immune cell state transitions and their link to clinical outcomes.
- There is a critical need to identify immunomodulatory programs that drive psoriasis progression.
Purpose of the Study:
- To investigate the unique immune cell profiles within the psoriasis niche compared to normal skin.
- To explore the developmental, metabolic, and intercellular communication abnormalities of T cells in psoriasis.
- To identify potential immunometabolic targets for psoriasis treatment.
Main Methods:
- Utilized single-cell RNA sequencing (RNA-seq) to analyze immune cell profiles in psoriasis lesions.
- Applied trajectory and pathway enrichment analysis to identify cellular abnormalities.
- Employed intercellular crosstalk modeling to understand cell-cell communication.
- Quantified T cell metabolism.
Main Results:
- Observed distinct immune cell profiles in the psoriasis niche, with increased infiltration of immunosuppressive regulatory T (Treg) cells and CTLA4+ CD8 T cells.
- Identified potential developmental and metabolic abnormalities in these suppressive T cells.
- Demonstrated that exhausted CTLA4+ CD8 T cells can signal via the CXCL13-CXCR3 ligand-receptor pair.
- Revealed enhanced metabolic activity in T cells within the psoriasis microenvironment.
Conclusions:
- Psoriasis involves significant cell-type specific reprogramming within the immune microenvironment.
- These findings provide evidence for immune-related biomarkers linked to psoriasis clinical outcomes.
- The study highlights the potential of targeting immunometabolism for novel psoriasis therapies.
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