Depletion of JunB in the Skin Causes Psoriasis-Like
Disease and Arthritis
Title: Psoriasis-like skin disease and arthritis
caused by inducible epidermal deletion of Jun proteins.
Authors: Zenz R, et al.
Publication: Nature. 2005 Sep 15;437(7057):369-75.
The authors reported that in psoriatic lesion, epidermal keratinocytes
(skin cells that produce keratin tissue) had decreased expression
of JunB gene, which had been genetically mapped to the psoriasis
susceptibility region PSORS6.
In an experiment, depletion of JunB and its companion c-Jun in
adult mice resulted in symptoms of psoriasis, including arthritic
lesion within 2 weeks.
For the development of arthritic lesion, T and B cells as well
as signaling through tumor necrosis factor receptor 1 (TNFR 1)
were required. The authors noted that prior to the onset of the
disease, two chemotactic proteins S100A8 and S100A9 were previously
mapped to psoriasis susceptibility region PSORS4. These proteins
were strongly induced in mutant keratinocyte cells.
The authors proposed that the depletion of JunB/activator protein
1 (AP-1) in keratinocyte trigger a chemokine/cytokine expression
(a type of immune response), which in turn result in localization
of neutrophils and macrophages to the skin thus resulting in psoriasis
symptoms.
The authors suggested that these changes in the skin were sufficient
to initiate both the skin lesion and the arthritis or joint pain
in psoriasis.
Editor’s Note: chemotactic proteins are proteins
that are involved in movement or cells along a chemical concentration
gradient, either toward or away from a chemical source.
Cytokine is a type of regulatory proteins that are released by
cells of the immune system as regulator of immune response. Chemokine
is a type of cytokine involved in inflammation. Neutrophil is
a type of white blood cell that can destroy microorganisms during
an immune reaction. Macrophage is a large cell that can engulf
or swallow and destroy foreign substances in the body.
