Interferons (IFNs) are now known to exert amultitude of immunological functions on both the innate and adaptive immunity. Given their pleiotropic effects on the immune system, it is conceivable that excess type I IFN or aberrant regulation of its signaling could contribute to autoimmunity. Several lines of evidence link IFNs to autoimmune disorders, in particular to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of a spectrum of genes that constitutes an "IFN signature" is the most significant observation indicating that IFNs may be dominant among the pathogenic mediators involved in some autoimmune diseases. A family of IFN-inducible genes, designated HIN-200 in the human and IFI-200 in the murine species, encodes evolutionary related human (IFI16, MNDA, AIM2, IFIX) and murine proteins (Ifi202 a, Ifi202b, Ifi203, Ifi204, Ifi205/D3). Physiological IFI16 expression was found in cells of the immune system, in endothelial cells, and in stratified squamous epithelia, such as skin. The presence of anti-IFI16 antibodies was reported in SLE and primary/secondary Sjögren's syndrome. More recently, we reported that anti-IFI16 autoantibodies differentiate limited cutaneous systemic sclerosis (lcSSc) from diffuse systemic sclerosis (dcSSc). Molecular studies performed in primary endothelial cells overexpressing IFI16 demonstrated that it may be involved in the early steps of inflammation by modulating endothelial cell function, such as expression of adhesion molecules and chemokine production, cell growth, and apoptosis. Moreover, here we report that IFI16 expression is induced by proinflammatory cytokines. In this article the role of the IFI16 protein and its corresponding autoantibodies in the etiopathogenesis of systemic autoimmune diseases, in which chronic inflammation is involved, are discussed.

Role of the Interferon-Inducible Gene IFI16 in the Etiopathogenesis of Systemic Autoimmune Disorders / M. Mondini, M. Vidali, P. Airò, M. De Andrea, P. Riboldi, P.L. Meroni, M. Gariglio, S. Landolfo. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 1110:(2007), pp. 47-56. [10.1196/annals.1423.006]

Role of the Interferon-Inducible Gene IFI16 in the Etiopathogenesis of Systemic Autoimmune Disorders

P. Riboldi;P.L. Meroni;
2007

Abstract

Interferons (IFNs) are now known to exert amultitude of immunological functions on both the innate and adaptive immunity. Given their pleiotropic effects on the immune system, it is conceivable that excess type I IFN or aberrant regulation of its signaling could contribute to autoimmunity. Several lines of evidence link IFNs to autoimmune disorders, in particular to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of a spectrum of genes that constitutes an "IFN signature" is the most significant observation indicating that IFNs may be dominant among the pathogenic mediators involved in some autoimmune diseases. A family of IFN-inducible genes, designated HIN-200 in the human and IFI-200 in the murine species, encodes evolutionary related human (IFI16, MNDA, AIM2, IFIX) and murine proteins (Ifi202 a, Ifi202b, Ifi203, Ifi204, Ifi205/D3). Physiological IFI16 expression was found in cells of the immune system, in endothelial cells, and in stratified squamous epithelia, such as skin. The presence of anti-IFI16 antibodies was reported in SLE and primary/secondary Sjögren's syndrome. More recently, we reported that anti-IFI16 autoantibodies differentiate limited cutaneous systemic sclerosis (lcSSc) from diffuse systemic sclerosis (dcSSc). Molecular studies performed in primary endothelial cells overexpressing IFI16 demonstrated that it may be involved in the early steps of inflammation by modulating endothelial cell function, such as expression of adhesion molecules and chemokine production, cell growth, and apoptosis. Moreover, here we report that IFI16 expression is induced by proinflammatory cytokines. In this article the role of the IFI16 protein and its corresponding autoantibodies in the etiopathogenesis of systemic autoimmune diseases, in which chronic inflammation is involved, are discussed.
Autoimmunity; Inflammation; Interferon-inducible gene IFI16; SLE; SSc; Systemic lupus erythematosus; Systemic sclerosis
Settore MED/16 - Reumatologia
Settore MED/09 - Medicina Interna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/33748
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