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Single-cell immune ecosystem and metabolism reprogramming imprinted by psoriasis niche.


ABSTRACT:

Background

A major challenge of psoriasis is its dysfunctional immune niche. Remarkable gaps remain in understanding how immune cell state transitions are linked to clinical outcomes in psoriasis. Thus, there is a pressing need to discover immunomodulatory programs governing psoriasis progression.

Methods

Here, by using the state-of-the-art single-cell RNA-sequencing (RNA-seq) data, we observed the unique immune cell profile inside the psoriasis niche compared with the normal skins.

Results

In detail, the immunosuppressive T cells such as regulatory T (Treg) cells and CTLA4+ CD8 T cells showed higher infiltration in the psoriasis niche, indicating the immunosuppressive state was imprinted by such disease. Interestingly, unbiased trajectory and pathway enrichment analysis showed that those suppressive T cells potentially showed developmental and metabolic abnormalities. Intercellular crosstalk modeling shows that exhausted CTLA4+ CD8 T cells can send out cytokine signaling via utilizing CXCL13-CXCR3 ligand-receptor pair. We finally quantified the metabolism profile of T cells and strikingly observed their enhanced metabolic activity.

Conclusions

Taken together, these data highlight cell-type specific reprogramming within the psoriasis microenvironment and provide evidence for immune-related biomarkers of psoriasis clinical outcome. Our work not only revealed the unique immune ecosystem of psoriasis, but also opened new opportunities for targeting immunometabolism in treating such skin diseases.

SUBMITTER: Jiang B 

PROVIDER: S-EPMC9403935 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Single-cell immune ecosystem and metabolism reprogramming imprinted by psoriasis niche.

Jiang Boxuan B   Zhang Han H   Wu Yingcheng Y   Shen Yu Y  

Annals of translational medicine 20220801 15


<h4>Background</h4>A major challenge of psoriasis is its dysfunctional immune niche. Remarkable gaps remain in understanding how immune cell state transitions are linked to clinical outcomes in psoriasis. Thus, there is a pressing need to discover immunomodulatory programs governing psoriasis progression.<h4>Methods</h4>Here, by using the state-of-the-art single-cell RNA-sequencing (RNA-seq) data, we observed the unique immune cell profile inside the psoriasis niche compared with the normal skin  ...[more]

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