CD8αα+T cells exert a pro-inflammatory role in patients with psoriasis

Y Y Zhang, Y T Lin, L Wang, X W Sun, E L Dang, K Xue, W G Zhang, K M Zhang, G Wang, B Li, Y Y Zhang, Y T Lin, L Wang, X W Sun, E L Dang, K Xue, W G Zhang, K M Zhang, G Wang, B Li

Abstract

Background: Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4+T cells, including Th17, Th1 and Th22. The role of CD8+T cells in psoriasis pathogenesis remains poorly understood.

Aim: To identify the phenotype of CD8+T cells in patients with psoriasis and to investigate its role in the formation of lesions.

Methods: The phenotype of CD8+T cells in psoriatic lesions was detected by immunofluorescence staining. Flow cytometry was performed to detect their phenotype in peripheral blood. Thereafter, coculture of CD8αα+T cells with autogenous CD4+T cells was performed to investigate the function of CD8αα+T cells in patients with psoriasis. Finally, pro-inflammatory factors produced by CD8αα+T cells were examined by immunofluorescence staining and flow cytometry.

Results: Compared to the CD8αβ+T cells, CD8αα+T cell infiltration in psoriatic lesions markedly increased. Moreover, epidermal CD8αα+T cells exhibited tissue-resident memory T cells (TRM) phenotypes and dermal CD8αα+T cells exhibited effector memory (TEM) phenotypes in psoriatic lesions. Additionally, we found that CD8αα+T cells from patients with psoriasis did not express the markers of regulatory T cells and could promote the proliferation of CD4+T effector cells and produce interleukin-17 and interferon-γ.

Conclusions: Our findings demonstrate that CD8αα+T cells contribute to the pathogenesis of psoriasis by producing pro-inflammatory factors.

Conflict of interest statement

The authors have no potential conflict of interest to declare.

© 2021 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Figures

FIGURE 1
FIGURE 1
(a–f) CD8αα+T cells increasingly infiltrate into psoriatic lesions. Representative immunofluorescence staining of CD8α co‐expressed with (a) TCRα, TCRδ and (b) CD8β in psoriatic lesions and normal skin. (c) Proportion of CD8αβ+T and CD8αα+T cells determined by analysis of immunofluorescence staining (n = 8). (d and e) Frequency of circulating CD8αβ+T and CD8αα+T cells (bottom) in gated CD3+CD8+T cells (up) from patients with psoriasis (n = 32) and healthy controls (n = 16). (f) Frequency correlation of circulating CD8αα+T cells with psoriasis area and severity index (PASI) scores of patients with psoriasis (n = 32). **p < 0.01
FIGURE 2
FIGURE 2
(a–d) Epidermal CD8αα+T cells exhibit TRM phenotypes. Representative immunofluorescence staining of (a) CD103 and (c) CD69 expressed in CD8αα+T cells of psoriatic lesions and normal skin. Proportion of (b) CD103+CD8+TRM and (d) CD69+CD8+TRM cells determined by analysis of immunofluorescence staining (n = 8). **p < 0.01
FIGURE 3
FIGURE 3
CD8αα+T cells do not express markers of Treg cells in psoriatic lesions. Representative immunofluorescence staining of Foxp3, CD25 and CD122 expressed in CD8αα+T cells of psoriatic lesions and normal skin
FIGURE 4
FIGURE 4
(a–c) CD8αα+T cells exhibit a pro‐inflammatory role in patients with psoriasis. (a) CD8αα+T cells from patients with psoriasis or healthy controls were cocultured with autogenetic CD4+T cells. Proliferation of CD4+T cells was detected by flow cytometry, which could reflect the function of CD8αα+T cells. (b) Statistical analysis of flow cytometry. (c) Mean difference of CD4+T cell proliferation (proportion of proliferated CD4+T cells in the coculture group minus that in the group of autogenetic CD4+T cells alone, n = 5). **p < 0.01
FIGURE 5
FIGURE 5
(a–f) CD8αα+T cells produce pro‐inflammatory factors in patients with psoriasis. (a) Representative immunofluorescence staining of IL‐17A and interferon‐γ (IFN‐γ) expressed in CD8αα+T cells of psoriatic lesions and normal skin. (b) Proportion of IL‐17A+ CD8αα+T and IFN‐γ+CD8αα+T cells determined by analysis of immunofluorescence staining (n = 8). (c) The expression of IL‐17A and (d) IFN‐γ in circulating CD8αα+T cells from patients with psoriasis (n = 32) and healthy controls (n = 16) by flow cytometry. (e and f) Statistical analysis of flow cytometry. *p < 0.05; **p < 0.01; ***p < 0.001

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