Sukseree, Supawadee, Bakiri, Latifa, Paloma-Irigoyen, Marta, Uluckan, Ozge, Petzelbauer, Peter and Wagner, Erwin (2021) Sequestosome 1/p62 enhances chronic skin inflammation. The Journal of allergy and clinical immunology. ISSN 10976825

Abstract

Background: The molecular control of inflammation and
epidermal thickening in skin lesions of patients with atopic
dermatitis (AD) is not known. Sequestosome 1/p62 is a
multifunctional adapter protein implicated in the control of key
regulators of cellular homeostasis, such as proinflammatory and
mechanistic target of rapamycin signaling.
Objective: We sought to determine whether p62 plays a role in
the cutaneous and systemic manifestations of an AD-like mouse
model.
Methods: AD-like skin lesions were induced by deletion of
JunB/AP-1, specifically in epidermal keratinocytes (JunBDep).
The contribution of p62 to pathological changes was determined
by inactivation of p62 in JunBDep p622/2 double knockout mice.
Results: Expression of p62 was elevated in skin lesions of
JunBDep mice, resembling upregulation of p62 in AD and
psoriasis. When p62 was inactivated, JunBDep-associated defects
in the differentiation of keratinocytes, epidermal thickening,
skin infiltration by mast cells and neutrophils, and the
development of macroscopic skin lesions were significantly
reduced. p62 inactivation had little effect on circulating
cytokines, but decreased serum IgE. Signaling through
mechanistic target of rapamycin and natural factor kappa B
was increased in JunBDep but not in JunBDep p622/2 double
knockout skin, indicating an important role of p62 in enhancing
these signaling pathways in the skin during AD-like
inflammation.

Item Type:	Article
Keywords:	AP-1 Atopic Dermatitis disease model mTOR NF-κB psoriasis sequestosome 1/p62 skin inflammation
Date Deposited:	22 Apr 2021 00:45
Last Modified:	22 Apr 2021 00:45
URI:	https://oak.novartis.com/id/eprint/43651