Interleukin-27 exerts a protective effect against psoriasis by inhibiting the secretion of interleukin-17A from T cells: a mechanistic study
- VernacularTitle:IL-27通过抑制T细胞分泌IL-17A在银屑病中发挥保护作用的机制研究
- Author:
Zhiyi LAN
1
;
Zeyu CHEN
;
Zihan ZHAO
;
Xilin ZHANG
;
Jun GU
;
Yuling SHI
Author Information
- Publication Type:Journal Article
- Keywords: Psoriasis; Interleukin-27; Interleukin-17; Th17 cells; Receptors, antigen, T-cell, gamma-delta
- From: Chinese Journal of Dermatology 2025;58(11):1034-1041
- CountryChina
- Language:Chinese
- Abstract: Objective:To investigate the specific mechanisms underlying the protective effect of interleukin (IL) -27 in the pathogenesis of psoriasis.Methods:Five skin tissue samples from healthy individuals and 6 lesional skin samples from psoriasis patients were collected, and IL-27 expression was determined by immunohistochemical staining. Il27ra gene knockout (KO) mice were constructed. Psoriasis-like mouse models were established with topical imiquimod in 5 wild-type (WT) mice and 6 KO mice. Mouse skin lesions were evaluated using the modified Psoriasis Area and Severity Index (mPASI), and lesional skin tissues were collected for hematoxylin and eosin (HE) staining to observe changes in epidermal thickness. Single-cell suspensions were prepared with skin lesions and skin-draining lymph nodes of 4 WT mice and 3 KO mice, and changes in immune cells (including T cells, γδ T cells, and neutrophils) were analyzed using flow cytometry. Additionally, skin-draining lymph node cells were isolated from 9 normal WT mice, and IL-17A expression was stimulated using a T-cell receptor agonist (CD3/28 activating antibodies, αCD3/28) or cytokines (IL-23 + IL-1β), followed by the addition of IL-27; peripheral blood mononuclear cells (PBMCs) were isolated from 6 psoriasis patients, and IL-17A expression was stimulated using the T-cell receptor agonist, followed by the addition of IL-27; the effect of IL-27 on IL-17A expression in T cells was analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Measurement data were compared between two groups using the t test. Results:Immunohistochemical staining revealed a significant reduction in IL-27 expression in psoriatic lesions (mean fluorescence intensity: 9.85 ± 3.07) compared with the normal skin (19.45 ± 2.51, t = 5.60, P < 0.001). Animal experiments demonstrated that the KO mice exhibited significantly aggravated psoriasis-like skin inflammation (mPASI: 4.00 ± 0.89) and significantly increased epidermal thickness (115.50 ± 7.69 μm) compared with the WT mice (mPASI: 2.80 ± 0.84, t = 2.28, P = 0.049; epidermal thickness: 92.26 ± 8.76 μm, t = 4.70, P = 0.001) ; compared with the WT mice, the KO mice showed significantly increased proportions of T cells (11.22% ± 2.76% vs. 7.08% ± 0.85%) and dermal γδ T cells (4.78% ± 0.39% vs. 2.78% ± 0.49%) among live cells in the lesions ( t = 2.91, 2.75, respectively, both P < 0.05), as well as significantly increased proportions of Th17, IL-17 + γδ T, Th22, and IL-22 + γδ T cells in the skin-draining lymph nodes (all P < 0.05), but no significant difference in the proportion of neutrophils in the lesions (WT: 13.57% ± 8.36%, KO: 14.43% ± 9.13%; t = 0.13, P = 0.902). Experiments with different stimuli showed that IL-27 significantly suppressed T-cell receptor agonist-induced IL-17A expression in murine γδ T cells (αCD3/28 group: 1.00 ± 0.11, αCD3/28 + IL-27 group: 0.76 ± 0.13; t = 3.54, P = 0.004), while there was no significant difference in IL-17A expression between cells induced by IL-23 + IL-1β with the IL-27 co-culture and those without ( t = 1.34, P > 0.05). ELISA showed that IL-27 significantly reduced the IL-17A concentration in the culture supernatant of draining lymph node cells stimulated by the T-cell receptor agonist (αCD3/28 group: 1 535.00 ± 97.76 pg/ml, αCD3/28 + IL-27 group: 1 030.00 ± 287.90 pg/ml, t = 3.29, P = 0.031), but did not reduce the IL-17A concentration induced by IL-23 + IL-1β ( t = 0.09, P > 0.05). Flow cytometry indicated that IL-27 significantly inhibited the T-cell receptor agonist-induced IL-17A expression in T cells from psoriasis patients (αCD3/28 group: 4.28 ± 3.25, αCD3/28 + IL-27 group: 3.04 ± 2.65, t = 4.46, P = 0.007) . Conclusion:IL-27 appeared to play a protective role in psoriasis by suppressing IL-17A secretion from T cells.
