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. 2013 Sep 26;15(5):R136.
doi: 10.1186/ar4317.

Th17 and Th22 cells in psoriatic arthritis and psoriasis

Helen Benham, Paul Norris, Jane Goodall, Mihir D Wechalekar, Oliver FitzGerald, Agnes Szentpetery, Malcolm Smith, Ranjeny Thomas, Hill Gaston

Th17 and Th22 cells in psoriatic arthritis and psoriasis

Helen Benham et al. Arthritis Res Ther. .

Abstract

Introduction: The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).

Methods: Flow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.

Results: Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.

Conclusions: Elevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.

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Figures

Figure 1
Figure 1
Frequency of interleukin-17+ and interleukin-22+CD4+ T cells in the peripheral blood mononuclear cells of patients with psoriatic arthritis patients with psoriasis and healthy controls. The frequency of interleukin 17 (IL-17)-positive CD4+ T cells (A) and IL-22-positive CD4+ T cells (C) in patients with psoriasis (Ps) or psoriatic arthritis (PsA) and healthy controls. The percentages of total CD4+ T cells are shown. Typical examples of intracellular staining of IL-17 (B) and IL-22 (D) are also shown after gating for CD3+CD4+ T cells. * p<0.05, **p<0.01, ***p<0.001 FSC = Forward Scatter.
Figure 2
Figure 2
Secretion of interleukin 17 and interleukin 22 by peripheral blood mononuclear cells from psoriatic arthritis and psoriasis patients and from healthy controls. The concentrations (Conc) of interleukin 17 (IL-17) (A) and IL-22 (B) in culture supernatants of peripheral blood mononuclear cells from patients with psoriasis (Ps) and patients with psoriatic arthritis (PsA) and from healthy controls four days after stimulation with anti-CD3/CD28. Correlations between percentages of IL-17+ and IL-22+CD4+ T cells and the concentrations of IL-17 (C) and IL-22 (D) in culture supernatants. * p<0.05, **p<0.01, ***p<0.001.
Figure 3
Figure 3
Coexpression of cytokines and chemokines by CD4+ T cells in peripheral blood mononuclear cells of psoriatic arthritis patients, psoriasis patients and healthy controls. Coexpression of interleukin 22 (IL-22) and interferon γ (IFNγ) by IL-17+CD4+ T cells (A). Coexpression of IL-17 and IFNγ by IL-22+CD4+ T cells (B). Expression of IL-23 receptor (IL-23R) by CD4+ T cells (C) and the proportions of CD4+IL-17+ T cells (D) and CD4+IL-22+ T cells (E) coexpressing IL-23R. Expression of chemokine receptor 6 (CCR6) and CCR4 by IL-17+ T cells (F) and (G) and by IL-22+ T cells (H) and (I) in psoriasis (Ps) patients and psoriatic arthritis (PsA) patients compared with healthy controls. Coexpression of CCR6 and CCR4 by CD4+IL-17+ T cells (J) and CD4+IL-22+ T cells (K). * p<0.05, **p<0.01, ***p<0.001.
Figure 4
Figure 4
Frequency of IL-17+ and IL-22 + CD4+ in skin resident T cells of psoriatic skin lesions compared to healthy skin and interleukin 23 receptor coexpression in skin, synovial fluid and peripheral blood of psoriasis and psoriatic arthritis patients. Frequency of interleukin 17-positive (IL-17+) and IL-22+CD4+ in psoriatic skin lesions compared to healthy skin (A) and (B). Frequency of IL-17+IL-22+CD4+ T cells in psoriatic skin lesions compared to healthy skin (C). Representative fluorescence-activated cell sorting plots demonstrating CD4+ T-cell expression of IL-22 and IL-17 in psoriatic versus healthy skin (D). Percentages of Th22 cells in psoriatic and healthy skin (E). Percentage of CD4+ T cells coexpressing IL-23 receptor (IL-23R) in paired synovial fluid (Syn) and peripheral blood (PB) from psoriatic arthritis (PsA) patients and in skin and PB of psoriasis (Ps) patients (F). * p<0.05, **p<0.01, ***p<0.001.
Figure 5
Figure 5
Frequency of CD4+IL-17+ T cells and CD4+IL-22+ T cells and coexpression of chemokine receptor 6 in synovial fluid and peripheral blood of psoriatic arthritis and rheumatoid arthritis patients. Frequency of CD4+IL-17+ T cells and CD4+IL-22+ T cells in psoriatic arthritis (PsA) synovial fluid (SF) and peripheral blood (PB) (A) and (B) and of CD4+IL-17+ and CD4+IL-22+ T cells in PsA and rheumatoid arthritis (RA) SF (C) and (D). Percentages of CD4+IL-17+ T-cell-expressing chemokine receptor 6 (CCR6) in PB and SF of patients with PsA (E). * p<0.05, **p<0.01, ***p<0.001.
Figure 6
Figure 6
Representative interleukin 17 and interleukin 22 expression patterns in synovial tissue from osteoarthritis, rheumatoid arthritis and psoriatic arthritis patients. (A) Positive cells show red staining; original magnification, ×200. (B) and (C) Semiquantitative (SQ) analysis shows grading of the percentage of cells present in entire tissue: 0 = no staining, 1 = <10%, 2 = 10% to 25%, 3 = 25% to 50% and 4 = >50% for both (B) interleukin 17-positive (IL-17+) and (C) IL-22+ in tissue samples from patients with osteoarthritis (OA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA). * p<0.05, **p<0.01, ***p<0.001.
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