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.

Signaling pathways and targeted therapies for psoriasis

“…35,36 Furthermore, recent studies also suggested that metabolic reprogramming is emerging as another crucial regulatory paradigm for psoriasis. [37][38][39] Extracellular cytokine pathways The TNF/IL-23/IL-17 pathway. The findings of a large number of genome-wide association studies (GWAS) and clinical trials support the central role of TNF-IL-23-IL-17 signaling pathways in the pathogenesis of psoriasis, especially for plaque psoriasis.…”

Characterization of the TCRβ repertoire of peripheral MR1-restricted MAIT cells in psoriasis vulgaris patients

“…Previous studies addressing TCRβ repertoire diversity in the context of psoriasis have been conducted in whole skin biopsy samples 38 – 40 , total peripheral mononuclear cells 41 and sorted cutaneous CD4 + T cell effector and regulatory T cells 42 , CD8 + 42 , 43 or CD45 + 44 T lymphocytes, providing little insight into the TCRβ clonotype diversity of MR1-restricted MAIT cells in PV. The MAIT TCR repertoire in healthy donors was most recently examined in single-cell TCRSeq settings, providing evidence for highly private, individually unique MAIT CDR3β sequences in the periphery 18 , while clonally expanded MAIT repertoire was primarily demonstrated in bone marrow, spleen and lungs, but not in healthy skin 45 .…”