TY - JOUR
T1 - A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin
AU - Johnson-Huang, Leanne M.
AU - Suárez-Fariñas, Mayte
AU - Pierson, Katherine C.
AU - Fuentes-Duculan, Judilyn
AU - Cueto, Inna
AU - Lentini, Tim
AU - Sullivan-Whalen, Mary
AU - Gilleaudeau, Patricia
AU - Krueger, James G.
AU - Haider, Asifa S.
AU - Lowes, Michelle A.
N1 - Funding Information:
This research was supported by a pilot project grant to ASH (Clinical and Translational Science Award grant UL 1RR024143); the Doris Duke Foundation supported LMJ-H and MAL; NIH K23 AR052404 also supported MAL; LMJ-H is also supported by the Linda and Leonard Berkowitz Postdoctoral Fellowship.
PY - 2012/4
Y1 - 2012/4
N2 - Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, which are important contributors to the inflammatory cascade in psoriatic lesions. To determine whether IFN-γ indeed induces the pathways expressed in psoriatic lesions, a single intradermal injection of IFN-γ was administered to an area of clinically normal, non-lesional (NL) skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-γ induced many molecular and histological features characteristic of psoriatic lesions. IFN-γ increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products tumor necrosis factor (TNF), inducible nitric oxide synthase, IL-23, and TNF-related apoptosis-inducing ligand were present in IFN-γ-treated skin. Thus, IFN-γ, which is significantly elevated in NL skin compared with healthy skin, appears to be a key pathogenic cytokine that can induce many features of the inflammatory cascade of psoriasis.
AB - Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, which are important contributors to the inflammatory cascade in psoriatic lesions. To determine whether IFN-γ indeed induces the pathways expressed in psoriatic lesions, a single intradermal injection of IFN-γ was administered to an area of clinically normal, non-lesional (NL) skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-γ induced many molecular and histological features characteristic of psoriatic lesions. IFN-γ increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products tumor necrosis factor (TNF), inducible nitric oxide synthase, IL-23, and TNF-related apoptosis-inducing ligand were present in IFN-γ-treated skin. Thus, IFN-γ, which is significantly elevated in NL skin compared with healthy skin, appears to be a key pathogenic cytokine that can induce many features of the inflammatory cascade of psoriasis.
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U2 - 10.1038/jid.2011.458
DO - 10.1038/jid.2011.458
M3 - Article
C2 - 22277938
AN - SCOPUS:84858283022
SN - 0022-202X
VL - 132
SP - 1177
EP - 1187
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -