Type I IFN and TNFα cross-regulation in immune-mediated inflammatory disease basic concepts and clinical relevance 英文参考文献.docVIP

Cantaert et al. Arthritis Research Therapy 2010,12:219 /content/12/5/219 RE VIE W Type I IFN and TNFα cross-regulation in immune-mediated in? ammatory disease: basic concepts and clinical relevance Tineke Cantaert, Dominique Baeten, Paul P Tak* and Lisa GM van Baarsen phos phorylation of signal transducers and activators of trans cription (STATs) and transcription of IFN response is results in resistance to viral replication, en- Abstract A cross-regulation between type I IFN and TNFα has been proposed recently, where both cytokines are hypothesized to counteract each other. According to this model, di?erent autoimmune diseases can be viewed as disequilibrium between both cytokines. As this model may have important clinical implications, the present review summarizes and discusses the currently available clinical evidence arguing for or against the proposed cross-regulation between TNFα and type I IFN. In addition, we review how this cross-regulation works at the cellular and molecular levels. Finally, we discuss the clinical relevance of this proposed cross-regulation for biological therapies such as type I IFN or anti-TNFα treatment. genes. hanced MHC class I expression and di? erentiation of monocytes, all of which contribute to clear infection. Besides an essential role in the host antiviral state, type I IFN has immuno regulatory functions by a? ecting cell proliferation and di? erentiation and by inducing anti- in? ammatory res ponses. Considering these important functions of type I IFN in normal homeostasis as well as host response, an aberrant function in type I IFN immunity may contribute to autoimmunity and chronic in? amma- is is illus trated by the observation that melanoma patients treated with IFNα2β developed clinical and sero- logical signs of autoimmunity [1] and that patients with a trisomy of chromosome 9, which contains the type I IFN genes, develop high IFN