Pellino-1 expression is associated with epidermal proliferation and enhanced Th17 cell infiltration in psoriatic lesions

• Published in: Experimental dermatology Vol. 32; no. 9; pp. 1476 - 1484
• Main Authors: Cho, Haeyon, Park, Nora Jee-Young, Ko, Jiwon, Lee, Chang-Woo, Lee, Jin-Kwan, Maeng, Young-In, Go, Heounjeong
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.09.2023
• Subjects: Biopsy; CD4 antigen; Cell proliferation; Epidermis; Foxp3 protein; GATA-3 protein; Helper cells; Infiltration; Inflammation; Lesions; Lymphocytes; Lymphocytes T; Psoriasis; Skin diseases; Therapeutic targets; epidermal proliferation; Pellino-1; Th17; psoriasis; T helper cell
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.14852

Pellino-1 plays a crucial role in cellular proliferation and regulates inflammatory processes. This study investigated Pellino-1 expression patterns and their relationship with CD4 T-cell subsets in psoriasis patients. Group 1 comprised primarily biopsied psoriasis lesions from 378 patients, multiplex-immunostained for Pellino-1, CD4 and representative T helper (Th) cells (T-bet [Th1], GATA3 [Th2], and RORγt [Th17] and regulatory T cell [FoxP3] markers). Ki-67 labeling was evaluated in the epidermis. Group 2 comprised 43 Pellino-1-positive cases immunostained for Pellino-1 in both lesion and non-lesion skin biopsy samples. Five normal skin biopsies served as controls. Among 378 psoriasis cases, 293 (77.5%) were positive for Pellino-1 in the epidermis. Pellino-1-positivity was higher in psoriasis lesions than in non-lesions and normal skin (52.55% vs. 40.43% vs. 3.48%, p < 0.001; H-score, 72.08 vs. 47.55 vs. 4.40, p < 0.001, respectively). Pellino-1-positive cases also had a significantly higher Ki-67 labeling index (p < 0.001). Epidermal Pellino1-positivity was significantly associated with higher RORγt (p = 0.001) and FoxP3 (p < 0.001) CD4 T cell ratios but not T-bet and GATA3 CD4 T cell ratios. Among the CD4 Pellino-1 T-cell subsets, the CD4 Pellino-1 RORγt ratio was significantly associated with epidermal Pellinio-1 expression (p < 0.001). Pellino-1 expression is thus increased in psoriasis lesions and associated with increased epidermal proliferation and CD4 T-cell subset infiltration, especially Th17 cells. This suggests that Pellino-1 could be a therapeutic target that simultaneously regulates psoriasis epidermal proliferation and immune interactions.