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Psoriasis and extra domain A fibronectin loops
Author(s) -
McFadden J.P.,
Baker B.S.,
Powles A.V.,
Fry L.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.09737.x
Subject(s) - proinflammatory cytokine , psoriasis , fibronectin , inflammation , immunology , tumor necrosis factor alpha , transforming growth factor , autocrine signalling , interleukin , cancer research , keratinocyte , medicine , cytokine , receptor , biology , microbiology and biotechnology , extracellular matrix , cell culture , genetics
Summary We have previously postulated that as well as T‐helper (Th) 1 and Th17 cells, the transforming growth factor (TGF)‐β/fibronectin (FN)/α5β1 pathway is central to psoriasis pathogenesis. EDA+ FN refers to an alternatively spliced isoform of FN with an additional domain known as extra domain A. EDA+ FN has two important properties pertinent to psoriasis lesions: it stimulates keratinocyte hyperproliferation, and, through stimulation of Toll‐like receptor (TLR) 4, stimulates production of proinflammatory cytokines. EDA+ FN production induced by TGF‐β stimulation can be maintained in psoriasis lesions via two main feedback loops. Firstly, EDA+ FN stimulates proliferation of keratinocytes, which, in an autocrine fashion, will release more EDA+ FN. Secondly, EDA+ FN stimulates TLR4 expressed by antigen‐presenting cells resulting in the production of proinflammatory cytokines such as tumour necrosis factor‐α, interleukin (IL)‐1, IL‐6 and IL‐12. The resultant promotion of cutaneous inflammation results in the recruitment of Th1 cells, which also produce EDA+ FN. We propose that these ‘FN loops’ contribute to the maintenance and progression of psoriatic lesions. Finally, although the association between psoriasis and heart/thrombotic disease remains unclear one plausible link may be the promotion of atherosclerosis and thrombotic heart disease by EDA+ FN.