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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-4-18
pubmed:abstractText
Cutaneous inflammation can show Th1 or Th2 predominance, but the precise mechanisms by which such selectivity is determined are unknown. A recent study has demonstrated that Th1 cells, but not Th2 cells, produce an endogenous ligand for Toll-like receptor (TLR) 4, namely extradomain A+ fibronectin containing extra type III domain A (FnEDA+). As TLR4 stimulation leads to production of proinflammatory cytokines that recruit (via altered endothelial adhesion molecule expression and chemokine production) more Th1/Th17 cells, a positive feedback mechanism for Th1/Th17 inflammation exists. We propose that FnEDA+ positive feedback loops are a potential driver of Th1/Th17 inflammation. Conversely, the inflammatory EDA+ fibronectin loop is negatively regulated in atopic dermatitis, Th2 cytokines actively suppress TLR4 expression of Th1 cytokines, and recruited Th2 cells do not produce FnEDA+. In psoriasis, there are multiple FnEDA+ loops, comprising inflammatory, keratinocyte, and autoimmune loops. In allergic contact dermatitis, a single inflammatory loop operates. In atopic dermatitis, the FnEDA+ loop is actively suppressed by Th2 cytokines, and recruited Th2 cells do not "feedback" FnEDA+. We review endogenous ligands for TLR in relation to inflammatory disease, FnEDA+ function, and the potential role for FnEDA+ in psoriasis, allergic contact dermatitis, and atopic dermatitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1879-1131
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-65
pubmed:meshHeading
pubmed:articleTitle
Extra domain A-positive fibronectin-positive feedback loops and their association with cutaneous inflammatory disease.
pubmed:affiliation
Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, SE1 7EH London, UK. john.mcfadden@kcl.ac.uk
pubmed:publicationType
Journal Article