Figure 1.
Macroscopic appearance of biopsied lesions from acne patients.
Table 1.
Clinical characteristics of acne patient group from Finland.
Table 2.
Clinical characteristics of acne patient group from Germany.
Figure 2.
2-components NMF (Non Negative Matrix Factorization) model.
The heatmap of 904 regulated genes on subjects-corrected log2-expressions (legend color blue for low expression and red for high expression).
Figure 3.
Bioinformatic analysis of differentially modulated genes.
Gene enrichment analysis in three different functional ontologies were performed using MetaCore: biological processes (a), process networks (b) and canonical pathway maps (c).
Table 3.
Top 20 up-regulated genes in the German acne patient group based on Affymetrix microarray technology.
Table 4.
Top 20 down-regulated genes in the German acne patient group based on Affymetrix microarray technology.
Figure 4.
Th17 related cytokines were increased in acne lesions.
The skin biopsies were obtained from healthy volunteers normal skin (NS), from acne patients non-lesional skin (A NS) and lesional skin (AL) and from psoriasis patients non-lesional skin (P NS) and lesional skin (PL). The expression levels of cytokines were determined by RT-PCR. The expressions of inflammatory cytokines TGF-β, IL-6, IL-1β and IL-23 were increased significantly both in acne and psoriasis but IL-1β and TGF-β expression was higher in acne. IL-23 was increased more in psoriasis lesions. IL-17A was significantly expressed in lesional acne and psoriasis skin. IL-22, was slightly elevated in acne and psoriasis, however significantly more in psoriasis. *P<0.05, **P<0.01, ***P<0.001; bars represent mean +SEM. RU, relative units; TGF-β, transforming growth factor- beta; Th17, T helper type 17.
Table 5.
Expression at the mRNA level of markers and cytokines characterizing the Th17 cell subtype in the German acne cohort.
Figure 5.
Inflammatory cell infiltrates of early acne lesions in immunohistochemistry.
Representative immunohistochemical staining showing IL-17A+ cells in early acne lesion (a). Staining of IL-17A+ and CD3+ cells shows that IL-17A (in green) and CD3 (in red) were detected in acne vulgaris lesions. Cell nuclei were counterstained in blue. Arrows indicate IL-17A and CD3 double positive cells (b). T-bet+ cells (c) were more numerous than IL-17A+ cells or Foxp3+ cells (d) in the lesional acne skin. Large number of CD4+ cells (e), mostly lymphocytes, was seen around pilosebaceous unit and perivascularly. CD8+ cells (f) were fewer in number than CD4+ cells. Large number of CD68+ macrophages (g) and a few CD83+ cells (h), which are mature dendritic cells, were detected around sebaceous follicles. (Bar = 200 µm; in the insets bar = 50 µm).
Table 6.
Expression at the protein level of markers and cytokines characterizing the Th17 cell subtype in the German acne cohort.
Table 7.
Number of positively stained cells in lesional and non-lesional skin of acne patients (n = 16)1 as assessed by immunohistochemistry.
Figure 6.
The expression of proinflammatory mediators in Finnish patient cohort examined by RT-PCR.
The expression of a) toll-like receptors TLR2 and TLR4, b) proinflammatory cytokine TNF-α and neutrophil chemotactic factor IL-8 were significantly up-regulated in lesional acne. c) IL-20 mRNA were increased in acne and psoriasis lesions. It is known that IL-20 can stimulate epidermal hyperplasia in model systems and is upregulated in psoriasis. *P<0.05, **P<0.01, ***P<0.001; bars represent mean ±SEM.
Table 8.
Expression at the mRNA level of proinflammatory mediators in the German acne cohort determined by Affymetrix microarray technology.
Figure 7.
Antimicrobial peptides are increased in acne and psoriasis lesions by RT-PCR.
The expressions of mRNAs were significantly higher in psoriasis except for hCAP-18, which was similarly expressed in both. *P<0.05, **P<0.01, ***P<0.001; bars represent mean ±SEM. BD2, human beta-defensin 2; BD3, human beta-defensin 3; hCAP-18, human cathelicidin antimicrobial protein 18; LCN2, lipocalin-2; RU, relative units.
Table 9.
Expression at the mRNA level of antimicrobial peptides in the German acne cohort determined by Affymetrix microarray technology.
Figure 8.
The expression of Th1 cell and Treg markers were activated in acne by RT-PCR.
Th1 transcription factor T-bet, Th1 cell surface chemokine receptor CXCR3 and IFN-γ (the effector cytokine of Th1 cells) mRNAs were significantly up-regulated in acne and psoriasis lesions. The transcription factor of Tregs, Foxp3, was elevated in acne and psoriasis. TGF-β which is both Th17 and Treg lineages inducing cytokine was significantly increased in acne lesions. The product of Tregs, immunosuppressive cytokine IL-10 was expressed more in acne than in psoriasis. *P<0.05, **P<0.01, ***P<0.001; bars represent mean ±SEM. RU, relative units; TGF-β, transforming growth factor- beta; Th1, T helper type 1; Treg, regulatory T cell.
Table 10.
Expression at the mRNA level of markers and cytokines characterizing the Th1 cell subtype in the German acne cohort determined by Affymetrix microarray technology.
Table 11.
Expression at the mRNA level of markers and cytokines characterizing the Treg cell subtype in the German acne cohort determined by Affymetrix microarray technology.
Figure 9.
The effect of IL-17 on keratinocytes.
Th17-cells are defined to secrete IL-17 cytokines. Also some other cells can secrete IL-17 cytokines when properly activated. IL-17A and IL-17F regulate genes on keratinocytes, that are involved in innate immune defence, such as antimicrobial peptides (beta-defensins, S100 proteins A7/9, cathelicidin, LCN2) and a range of chemokines G-CSF, CXCLs and CCL20 which regulate neutrophil and lymphocyte trafficking. IL-17A and IL-17F stimulate keratinocytes leading to keratinocyte proliferation. Also vascular inflammation is activated.