Interleukin-4 and interleukin-13 as possible therapeutic targets in systemic sclerosis.

Interleukin-4 and interleukin-13 as possible therapeutic targets in systemic sclerosis. Cytokine. 2019 Aug 07;125:154799 Authors: Gasparini G, Cozzani E, Parodi A 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 t...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research