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Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis.

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, Teunissen MB - PLoS ONE (2010)

Bottom Line: Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin.Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin.Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.c.res@amc.uva.nl

ABSTRACT

Background: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ.

Methodology/principal findings: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

Conclusions/significance: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.

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Proportions of IL-17A and IL-22 producing T cells in the epidermis versus dermis.The increase in the percentages of Tc17 and IL-22 producing CD8 T cells is even more pronounced in the psoriatic epidermis than in the psoriatic dermis, whereas normal epidermis and dermis are almost devoid of such T cells (n = 4).
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pone-0014108-g004: Proportions of IL-17A and IL-22 producing T cells in the epidermis versus dermis.The increase in the percentages of Tc17 and IL-22 producing CD8 T cells is even more pronounced in the psoriatic epidermis than in the psoriatic dermis, whereas normal epidermis and dermis are almost devoid of such T cells (n = 4).

Mentions: When the cytokine profiles of dermal CD4 and CD8 T cell subsets were analyzed separately, we found, surprisingly, that the proportions of Th17 cells were very similar in psoriatic dermis compared to normal dermis (Figure 3A). This held true for Th17 cells that only produced IL-17A (psoriatic skin: 5.94%±1.13; normal skin: 5.87%±1.83%) and for Th17 cells that coproduced IL-22 (psoriatic skin: 2.36%±0.72%; normal skin: 2.05%±0.95%) or IFN-γ (psoriatic skin: 0.33%±0.12%; normal skin: 0.84%±0.41%). Obviously, in contrast to the percentage, the absolute number of Th17 cells is still much higher in psoriatic skin as it is more densely populated with T cells [6]. In both psoriasis patients and healthy individuals the total percentage of Th17 cells exceeded that of Tc17 cells (psoriatic skin: Th17 8.89%±1.88%, Tc17 3.39%±0.70%; normal skin: Th17 9.18%±3.13%; Tc17 0.35%±0.17%), which is consistent with our data on IL-17A expression by T cells in peripheral blood (unpublished observation). Remarkably, the dermal CD8 T cell population from psoriatic skin contained a significantly increased percentage of Tc17 cells (psoriatic skin: 3.39%±0.70%; normal skin: 0.35%±0.17%). This was not only the case for the IL-17A single producers, but also for Tc17 cells coproducing IL-22 (Figure 3B). Moreover, and further underlining a possible role of Tc17 cells in the pathogenesis of psoriasis, the epidermis contained an even 2 to 10 fold higher frequency of Tc17 cells than the adjacent dermis. This was observed in all four psoriasis patients from whom we had obtained enough epidermal T cells for analysis (Figure 4). In contrast, the population of T cells derived from the epidermis and adjacent dermis of normal skin contained similar low levels of Tc17 cells. Th17 cells were present in substantial numbers in the epidermis from both psoriatic and normal skin, but no consistent pattern of increase/decrease relative to the corresponding dermis was observed (Figure 4).


Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis.

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, Teunissen MB - PLoS ONE (2010)

Proportions of IL-17A and IL-22 producing T cells in the epidermis versus dermis.The increase in the percentages of Tc17 and IL-22 producing CD8 T cells is even more pronounced in the psoriatic epidermis than in the psoriatic dermis, whereas normal epidermis and dermis are almost devoid of such T cells (n = 4).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991333&req=5

pone-0014108-g004: Proportions of IL-17A and IL-22 producing T cells in the epidermis versus dermis.The increase in the percentages of Tc17 and IL-22 producing CD8 T cells is even more pronounced in the psoriatic epidermis than in the psoriatic dermis, whereas normal epidermis and dermis are almost devoid of such T cells (n = 4).
Mentions: When the cytokine profiles of dermal CD4 and CD8 T cell subsets were analyzed separately, we found, surprisingly, that the proportions of Th17 cells were very similar in psoriatic dermis compared to normal dermis (Figure 3A). This held true for Th17 cells that only produced IL-17A (psoriatic skin: 5.94%±1.13; normal skin: 5.87%±1.83%) and for Th17 cells that coproduced IL-22 (psoriatic skin: 2.36%±0.72%; normal skin: 2.05%±0.95%) or IFN-γ (psoriatic skin: 0.33%±0.12%; normal skin: 0.84%±0.41%). Obviously, in contrast to the percentage, the absolute number of Th17 cells is still much higher in psoriatic skin as it is more densely populated with T cells [6]. In both psoriasis patients and healthy individuals the total percentage of Th17 cells exceeded that of Tc17 cells (psoriatic skin: Th17 8.89%±1.88%, Tc17 3.39%±0.70%; normal skin: Th17 9.18%±3.13%; Tc17 0.35%±0.17%), which is consistent with our data on IL-17A expression by T cells in peripheral blood (unpublished observation). Remarkably, the dermal CD8 T cell population from psoriatic skin contained a significantly increased percentage of Tc17 cells (psoriatic skin: 3.39%±0.70%; normal skin: 0.35%±0.17%). This was not only the case for the IL-17A single producers, but also for Tc17 cells coproducing IL-22 (Figure 3B). Moreover, and further underlining a possible role of Tc17 cells in the pathogenesis of psoriasis, the epidermis contained an even 2 to 10 fold higher frequency of Tc17 cells than the adjacent dermis. This was observed in all four psoriasis patients from whom we had obtained enough epidermal T cells for analysis (Figure 4). In contrast, the population of T cells derived from the epidermis and adjacent dermis of normal skin contained similar low levels of Tc17 cells. Th17 cells were present in substantial numbers in the epidermis from both psoriatic and normal skin, but no consistent pattern of increase/decrease relative to the corresponding dermis was observed (Figure 4).

Bottom Line: Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin.Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin.Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.c.res@amc.uva.nl

ABSTRACT

Background: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ.

Methodology/principal findings: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

Conclusions/significance: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.

Show MeSH
Related in: MedlinePlus