Effective Narrow-Band UVB Radiation Therapy Suppresses the IL-23/IL-17 Axis in Normalized Psoriasis Plaques Leanne M. Johnson-Huang, Mayte Suárez-Fariñas,

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Effective Narrow-Band UVB Radiation Therapy Suppresses the IL-23/IL-17 Axis in Normalized Psoriasis Plaques Leanne M. Johnson-Huang, Mayte Suárez-Fariñas, Mary Sullivan-Whalen, Patricia Gilleaudeau, James G. Krueger, Michelle A. Lowes Journal of Investigative Dermatology Volume 130, Issue 11, Pages 2654-2663 (November 2010) DOI: 10.1038/jid.2010.166 Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Classification of normalized and nonresponsive plaques. (a, b) Histological response was measured at baseline in non-lesional (NL) and lesional (LS) skin and skin at 6 weeks after treatment (week 6). Representative histology and immunohistochemistry showing hematoxylin and eosin (H&E) and K16 expression in (a) normalized plaques and (b) nonresponsive plaques. Scale bar=100μm. (c) Epidermal thickness of normalized (black bars, n=7) and nonresponsive plaques (white bars, n=6) before and after NB-UVB therapy. Error bars represent the mean±SEM. NL and week 6 values are compared with LS. ***P<0.001. (d) K16 mRNA expression normalized to hARP in both normalized (black bars) and nonresponsive plaques (white bars). Error bars represent the mean±SEM. Journal of Investigative Dermatology 2010 130, 2654-2663DOI: (10.1038/jid.2010.166) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Inflammatory myeloid dendritic cells (DCs) are reduced in normalized plaques. (a, b) Representative immunohistochemistry of CD1c+ and CD11c+ cells. Bar=100μm. (c, d) Quantification of dermal CD1c+ or CD11c+ cells in normalized (black) and nonresponsive plaques (white). Each circle represents a plaque. Non-lesional (NL) and week 6 values are compared with lesional (LS) skin values. **P<0.01, ***P<0.001. (e) CD11c+CD1c− cell numbers were calculated by subtracting CD1c+ counts from CD11c+ counts. (f) Two-color immunofluorescence of CD11c (green) and CD1c (red) of normalized plaque. Cells coexpressing both markers appear yellow because of the superimposition of both green and red signals. Inset, high-power magnification of double-positive cells. The white line delineates the dermoepidermal junction. Scale bar=100μm. Journal of Investigative Dermatology 2010 130, 2654-2663DOI: (10.1038/jid.2010.166) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Decreased dendritic cell (DC) products in normalized plaques. (a) mRNA expression levels normalized to hARP for the inflammatory DC products, inducible nitric oxide synthase (iNOS), IL-20, IL-12/23p40, and IL-23p19, in both normalized (black bars, n=8) and nonresponsive plaques (white bars, n=6). Error bars represent the mean±SEM. Non-lesional (NL) and week 6 levels are compared with lesional (LS) skin levels. *P<0.05, **P<0.01, ***P<0.001. (b, c) Two-color immunofluorescence of CD11c+ myeloid DCs (red) with IL-23 subunits in a normalized plaque, (b) p40 and (c) p19 (green), showing coexpression in baseline LS skin (yellow cells), which is diminished by week 6 after therapy. Antibodies conjugated with a fluorochrome gave background epidermal fluorescence. The white line delineates the dermal epidermal junction. Inset, high-power magnification of double-positive cells. Scale bar=100μm. Journal of Investigative Dermatology 2010 130, 2654-2663DOI: (10.1038/jid.2010.166) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 T cells are reduced in normalized plaques. (a) Representative immunohistochemistry of CD3+ cells in non-lesional (NL), lesional (LS), and week 6 skin of a normalized plaque. Scale bar=100μm. (b) Quantification of CD3+ T-cell counts per mm of skin in both normalized (black circles) and nonresponsive plaques (white circles). NL and week 6 counts are compared with LS skin counts. **P<0.01, ***P<0.001. (c) Response scores were correlated with μ-scores for CD3+ cell counts. Spearman's correlation coefficients (r) and P-values are shown. Journal of Investigative Dermatology 2010 130, 2654-2663DOI: (10.1038/jid.2010.166) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Decreased IL-17 and IL-22 after therapy. (a) mRNA expression levels normalized to hARP for the T-cell products, IL-17, IFN-γ, and IL-22, in both normalized (black bars, n=8) and nonresponsive plaques (white bars, n=6) in non-lesional (NL), lesional (LS), and week 6 skin. Error bars represent the mean±SEM. NL and week 6 levels are compared with LS skin levels. **P<0.01, ***P<0.001. (b) Response scores were correlated with μ-scores for mRNA expression. Spearman's correlation coefficients (r) and P-values are shown. Journal of Investigative Dermatology 2010 130, 2654-2663DOI: (10.1038/jid.2010.166) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions