Interleukin-4 and interleukin-13 as possible therapeutic targets in systemic sclerosis.
Cytokine
; 125: 154799, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31400638
ABSTRACT
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs. Its pathogenesis, which is still poorly understood, features three main pathogenic moments an initial diffuse vasculopathy followed by low-grade inflammation and a subsequent tissue fibrosis. Numerous evidences support the role of a Th2-oriented immune response during both the inflammatory and the fibrotic phase of SSc. Levels of IL-4, IL-13 and CXCL4 are higher in the serum of SSc patients compared to healthy controls. Fibrotic tissue in SSc displays a Th2 polarized CD4+ cell infiltration, influencing fibroblast phenotype and inducing collagen and extra cellular matrix protein synthesis. In tight skin mice the administration of neutralizing anti-IL-4 antibodies prevents the development of dermal fibrosis. Back-crossing these mice onto a genetic background that cannot respond to IL-4 prevents skin sclerosis. In SSc, CD8+ T lymphocytes secrete IL-13 and mediate dermal fibrosis and have skin-homing receptors. Incubation with healthy dermal fibroblasts results in elevation of extracellular matrix, which can be reduced with anti-IL13 antibodies. Specifically, IL-4 and IL-13 take part in the inflammatory phase, contribute to the transition from the inflammatory to the fibrotic phase and maintain a profibrotic state in affected organs, mediating the interaction between T cells and fibroblasts. Blocking the cross-talk between these cell types by acting on the soluble cytokines, on their receptors on cell surfaces or on intracellular signaling pathways could constitute a new therapeutic approach.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
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Transdução de Sinais
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Interleucina-4
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Células Th2
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Interleucina-13
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article