Signs of innate immune activation and premature immunosenescence in psoriasis patients

Abstract

Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors. Innate immune activation is indicated by increased absent in melanoma 2 (AIM2) inflammasome gene expression and active caspase 1 staining in psoriatic lesional skin. Increased eomesodermin (EOMES) expression in lesional and non-lesional skin is suggestive of innate-like virtual memory CD8+ T cell infiltration. We found that signs of systemic inflammation were present in most of the patients, correlated with the severity of the disease, and pointed to IL-6 involvement in the pathogenesis of psoriatic arthritis. Among the circulating T cell subpopulations, we identified a higher proportion of terminally differentiated or senescent CD8+ T cells, especially in patients with long disease duration, suggesting premature immunosenescence and its possible implications for psoriasis co-morbidities.

Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies

“…We detected numerous T cell phenotypes and sub-phenotypes across inflammatory skin conditions by using Seq-Well S 3 . Among multiple psoriasis biopsies, we observed over-representation of Tregs, dysfunctional NR4A1 -expressing T cells, and senescent SESN3 + T cells, which could reflect a role for broader T cell dysfunction in disease pathology ( Šahmatova et al., 2017 ). Meanwhile, in leprosy, we identified a population of T cells enriched for expression of ROR-γT , consistent with a suggested role for Th-17 cells in bacterial control ( Saini et al., 2013 ; Saini et al., 2016 ).…”

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China

“…Psoriasis is a widespread autoimmune disease and systemic inflammatory disorder with which many of comorbidities (e.g., diabetes, cardiovascular diseases, Crohn's disease, lymphoma, and cancer) are associated. Patients with psoriasis tend to have an increased risk of cancer [16]. Single nucleotide polymorphisms (SNPs) influence the expression or the activities of caspase enzymes.…”

Evaluation of skin-surface interleukin 1 alpha, interleukin-1 Receptor Antagonist, CXCL-1/2 and beta-defensin-1 as non-invasive biomarkers for monitoring psoriasis vulgaris

“…IL-1α and IL-1RA are examples of a pro-in ammatory and anti-in ammatory interleukins, respectively, that are known to play important roles in skin homeostasis and skin in ammation, including psoriasis 36−40; 43 . The combination of chemokines CXCL-1 and − 2 was chosen because of their roles in attracting neutrophils to psoriatic skin lesions 38,41 . The anti-microbial peptide hBD-1 was chosen as a representative of beta-defensins in psoriasis 44,45 .…”