IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses.
Cell Differentiation
Cells, Cultured
Dermatitis, Atopic
/ etiology
Epidermis
/ pathology
Humans
Inflammation
/ etiology
Interleukin-1 Receptor-Associated Kinases
/ physiology
NF-kappa B
/ physiology
Psoriasis
/ etiology
Severity of Illness Index
Signal Transduction
Transcription Factors
/ physiology
Tumor Suppressor Proteins
/ physiology
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
23
12
2020
revised:
01
03
2021
accepted:
16
03
2021
pubmed:
18
4
2021
medline:
15
12
2021
entrez:
17
4
2021
Statut:
ppublish
Résumé
Many inflammatory skin diseases are characterized by altered epidermal differentiation. Whether this altered differentiation promotes inflammatory responses has been unknown. Here, we show that IRAK2, a member of the signaling complex downstream of IL-1 and IL-36, correlates positively with disease severity in both atopic dermatitis and psoriasis. Inhibition of epidermal IRAK2 normalizes differentiation and inflammation in two mouse models of psoriasis- and atopic dermatitis-like inflammation. Specifically, we demonstrate that IRAK2 ties together proinflammatory and differentiation-dependent responses and show that this function of IRAK2 is specific to keratinocytes and acts through the differentiation-associated transcription factor ZNF750. Taken together, our findings suggest that IRAK2 has a critical role in promoting feed-forward amplification of inflammatory responses in skin through modulation of differentiation pathways and inflammatory responses.
Identifiants
pubmed: 33864770
pii: S0022-202X(21)01139-8
doi: 10.1016/j.jid.2021.03.019
pmc: PMC9423738
mid: NIHMS1736470
pii:
doi:
Substances chimiques
NF-kappa B
0
Transcription Factors
0
Tumor Suppressor Proteins
0
ZNF750 protein, human
0
Interleukin-1 Receptor-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2436-2448Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR073196
Pays : United States
Organisme : NIAMS NIH HHS
ID : K08 AR060802
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR044882
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075047
Pays : United States
Organisme : NIAMS NIH HHS
ID : P50 AR070590
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR040312
Pays : United States
Organisme : NIAMS NIH HHS
ID : L40 AR076139
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR072773
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069071
Pays : United States
Organisme : NIAMS NIH HHS
ID : P50 AR080594
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075043
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR072129
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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