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

Author:

Cho Haeyon1,Park Nora Jee‐Young2345,Ko Jiwon16,Lee Chang‐Woo78,Lee Jin‐Kwan78,Maeng Young‐In9,Go Heounjeong1ORCID

Affiliation:

1. Department of Pathology, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea

2. Department of Pathology, School of Medicine Kyungpook National University Daegu Republic of Korea

3. Department of Pathology Kyungpook National University Chilgok Hospital Daegu Republic of Korea

4. BK21 Four Program, School of Medicine Kyungpook National University Daegu Republic of Korea

5. Clinical Omics Institute, Kyungpook National University Daegu Republic of Korea

6. Asan Institute for Life Science, University of Ulsan College of Medicine Asan Medical Center Seoul Republic of Korea

7. Department of Molecular Cell Biology, Samsung Medical Center Sungkyunkwan University School of Medicine Suwon Republic of Korea

8. Research Institute, Curogen Co., Ltd. Suwon Republic of Korea

9. Department of Pathology, School of Medicine Catholic University of Daegu Daegu Republic of Korea

Abstract

AbstractPellino‐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.

Publisher

Wiley

Subject

Dermatology,Molecular Biology,Biochemistry

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