Scleroderma

Danilo Bretas de Oliveira, Gabriel Magno de Freitas Almeida, Antonio Carlos Martins Guedes, Flavia Patrıcia Sena Teixeira Santos, Claudio Antonio Bonjardim, Paulo Cesar Peregrino Ferreira, and Erna Geessien Kroon
Received 15 June 2011; Revised 10 August 2011; Accepted 23 August 2011

Systemic sclerosis (SSc) is a complex autoimmune disease of unknown aetiology characterized by excessive fibrosis of the skin and internal organs, presence of autoantibodies to nuclear antigens, and vascular damage. Several genetic and environmental agents have been proposed to be responsible for causing SSc.

Among these agents are infections, toxin exposure, single nucleotide polymorphisms (SNPs), and interferon treatment. Regardless of the origin, the immune system on SSc patients shows evidence of homeostatic alterations, including increased levels of chemokines in blood serum and different populations of lymphocytes in peripheral blood mononuclear cells (PBMCs). In addition to these alterations, there is increased evidence that the interferon (IFN) system is modified in patients with SSc.

IFNs are immunomodulatory cytokines that act as an important link between the innate and adaptive immune system in vertebrates. IFNs bind to distinct cellular receptors, and their biological activities are mediated by the regulation of interferon stimulated genes (ISGs). IFNs can be divided into three types based on receptor binding and homology. Type I and type III IFNs are important regulators of innate immunity and are produced after stimulation of pattern recognition receptors in order to initiate and regulate the immune response.

One of the main pathways leading to type I and III IFNs induction depends on the induction and activation of IRF7. Almost every cell type is able to produce these IFNs after stimulation, but its main producers are cells from the immune system such as plasmacytoid dentritic cells. Type I and III IFNs have redundant biological activities, even though they bind to different cellular receptors and have distinct structures.

IFN gamma, the only known type II IFN, has distinct biological activities and is important for the regulation of adaptive immunity. The innate immune system and type I IFNs have been proposed as important factors in the initiation and maintenance of some autoimmune diseases, and the influence of type I IFNs in SSc has not been studied in detail. Several activities of type I and type III IFNs are redundant, and until now there has been no description of type III IFNs participation in SSc or other autoimmune diseases. An SNP in one chain of the type III IFN receptor (IL10R2) has been associated with SSc, indicating that at least responsivity to these molecules may be important for the disease.

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