Photo Credit: Andreus
The following is a summary of “FC03 T17 polarization of skin-homing (CLA-positive) T cells is maintained by activation-dependent, AP-1-mediated chromatin remodelling,” published in the December 2024 issue of Dermatology by Zhang et al.
Researchers conducted a retrospective study to investigate the polyclonal expansion and persistence of ‘driver clones’ in T cells in psoriasis and PsA after effective treatment.
They stimulated PBMCs from 85 individuals with psoriasis and 68 controls for 24 hours using anti-CD3/CD28 Dynabeads or without beads (0 h). On Day 0 or Day 1, cells were flow sorted (CD3+CD45RO+, CD4/CD8 × CLA+/CLA- × 0/24 h), followed by RNA-seq and ATAC-seq.
The results showed the CD3/CD28 activation led to a >100-fold increase in T17 signature transcripts IL17A, IL17F, IL22, and CCL22, as well as the T1 transcript IFNG. The stratified analysis revealed a 2.9- to 12.1-fold increase in the T17 signature mRNAs in activated T cells without a corresponding rise in IFNG. The IL17A and IL17F were overexpressed in activated T cells from psoriatic donors, with a 1.9-fold increase (P = 4.7E−4). CENTIPEDE analysis of 702 transcription factor (TF) motifs showed strong correlations between activation (CLAN at 24 vs 0 h) and skin-homing status (CLAP vs CLAN at 0 h) [Spearman’s rho = 0.94 for CD4, 0.93 for CD8]. Activation correlations were weaker for CD8/CD4 (rho = 0.41 for CLAN, 0.29 for CLAP). AP-1 motifs were notably enriched in CLAP vs CLAN differential motifs (P < 2.2E−16 for CD4 and CD8, Fisher’s exact).
Investigators concluded the CLAP as effector memory T cells (Tem) from skin or tonsil injury/infection, while CLAN as central memory T cells (Tcm) that might arise in multiple tissues; the findings support that Th17 cells were long-lived Tem, with increased responsiveness driven by AP-1 TF occupancy, and suggested that repetitive activation of memory T cells might explain polyclonal T cell presence in psoriasis lesions.
Source: academic.oup.com/bjd/article/191/Supplement_3/ljae360.003/7916064
