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A Single Intradermal Injection of IFN-γ Induces an Inflammatory State in Both Non- Lesional Psoriatic and Healthy Skin  Leanne M. Johnson-Huang, Mayte.

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Presentation on theme: "A Single Intradermal Injection of IFN-γ Induces an Inflammatory State in Both Non- Lesional Psoriatic and Healthy Skin  Leanne M. Johnson-Huang, Mayte."— Presentation transcript:

1 A Single Intradermal Injection of IFN-γ Induces an Inflammatory State in Both Non- Lesional Psoriatic and Healthy Skin  Leanne M. Johnson-Huang, Mayte Suárez-Fariñas, Katherine C. Pierson, Judilyn Fuentes-Duculan, Inna Cueto, Tim Lentini, Mary Sullivan-Whalen, Patricia Gilleaudeau, James G. Krueger, Asifa S. Haider, Michelle A. Lowes  Journal of Investigative Dermatology  Volume 132, Issue 4, Pages (April 2012) DOI: /jid Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 IFN-γ injection induces genomic expression of known IFN-γ–regulated chemokines. mRNA expression levels normalized to human acidic ribosomal protein (hARP) for the T-cell (CXCL9 and CXCL10) and dendritic cell (DC; CCL2 and CX3CL1) chemokines in baseline, placebo, and IFN-γ-injected healthy (black bars, n=10) and psoriatic skin (white bars, n=10). Error bars represent the mean±SEM. IFN-γ-injected skin was compared with placebo. **P<0.01. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 IFN-γ injection induces dermal inflammatory myeloid dendritic cells (DCs). Representative immunohistochemistry of (a) CD11c+ and (b) CD1c+ cells in psoriatic skin. (c) Quantification of CD11c+, CD1c+, and inflammatory DCs (CD11c+ minus CD1c+ cells) in healthy (black circles) and psoriatic skin (white circles). Each circle represents a different patient. IFN-γ-injected skin is compared with placebo. ***P< (d) Two-color immunofluorescence of CD1c+ DCs (red) and CD11c+ DCs (green). The white line delineates the dermal–epidermal junction. Bar=100μm. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 IFN-γ injection induces expression of known products of inflammatory myeloid dendritic cells (DCs). Two-color immunofluorescence of CD11c+ DCs with inflammatory products: (a) tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), (b) TNF, and (c) inducible nitric oxide synthase (iNOS) in baseline, placebo, and IFN-γ-injected psoriatic skin. The white line delineates the dermal–epidermal junction. Bar=100μm. (d) mRNA expression levels normalized to human acidic ribosomal protein (hARP) for additional DC cytokines in healthy (black bars, n=10) and psoriatic skin (white bars, n=10). Error bars represent the mean±SEM. IFN-γ-injected skin is compared with placebo. *P<0.05, **P<0.01. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 IFN-γ injection induces lymphoid-like structures and expression of known lymphoid genes and proteins. (a) mRNA expression levels normalized to human acidic ribosomal protein (hARP) for the lymphoid genes in healthy (black bars, n=10) and psoriatic skin (white bars, n=10). Error bars represent the mean±SEM. IFN-γ-injected skin is compared with placebo. **P<0.01, ***P< (b) Two-color immunofluorescence of CD11c+ dendritic cells (DCs; red) and CD3+ T cells (green) in psoriatic skin. White arrows denote DC/T-cell clusters. The white line delineates the dermal–epidermal junction. Representative immunohistochemistry of (c) peripheral node addressin (PNAd) and (d) ICAM-1 in psoriatic skin. Bar=100μm. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 The gradient of IFN-γ mRNA expression parallels T-cell and dendritic cell (DC) infiltration as psoriasis becomes more severe. (a) IFN-γ mRNA expression in healthy (n=10), non-lesional (NL) skin from mild (n=10, body surface area (BSA) <10%) versus moderate-to-severe (n=9, BSA>10%) psoriasis patients, IFN-γ-injected healthy (n=10) or mild NL psoriatic (n=10) skin, and psoriatic lesional (LS; n=9) skin. Error bars represent the mean±SEM. **P<0.01. ***P< (b) Quantification of CD3+ T cell (blue bars) and CD11c+CD1c- inflammatory DC (red bars) counts per mm of skin in patients in a. Mod, moderate; NS, nonsignificant. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

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