The control of tissue fibrosis by the inflammatory molecule LIGHT (TNF Superfamily member 14).
Pharmacol Res
; 104: 151-5, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26748035
ABSTRACT
The TNF Superfamily member LIGHT (TNFSF14) has recently emerged as a potential target for therapeutic interventions aiming to halt tissue fibrosis. In this perspective, we discuss how LIGHT may influence the inflammatory and remodeling steps that characterize fibrosis, relevant for many human diseases presenting with scarring such as asthma, idiopathic pulmonary fibrosis, systemic sclerosis, and atopic dermatitis. LIGHT acts through two receptors in the TNF receptor superfamily, HVEM (TNFRSF14) and LTßR (TNFRSF3), which are broadly expressed on hematopoietic and non-hematopoietic cells. LIGHT can regulate infiltrating T cells, macrophages, and eosinophils, controlling their trafficking or retention in the inflamed tissue, their proliferation, and their ability to produce cytokines that amplify fibrotic processes. More interestingly, LIGHT can act on structural cells, namely epithelial cells, fibroblasts, smooth muscle cells, adipocytes, and endothelial cells. By signaling through either HVEM or LTßR expressed on these cells, LIGHT can contribute to their proliferation and expression of chemokines, growth factors, and metalloproteinases. This will lead to hyperplasia of epithelial cells, fibroblasts, and smooth muscle cells, deposition of extracellular matrix proteins, vascular damage, and further immune alterations that in concert constitute fibrosis. Because of its early expression by T cells, LIGHT may be an initiator of fibrotic diseases, but other sources in the immune system could also signify a role for LIGHT in maintaining or perpetuating fibrotic activity. LIGHT may then be an attractive prognostic marker as well as an appealing target for fibrosis therapies relevant to humans.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article