Interferons as pathogenic effectors in autoimmunity

• Published in: Immunological reviews Vol. 204; no. 1; pp. 9 - 26
• Main Authors: Baccala, Roberto, Kono, Dwight H., Theofilopoulos, Argyrios N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01.04.2005; Blackwell
• Subjects: Animals; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity - immunology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; General aspects; Humans; Immunopathology; Interferons - immunology; Interferons - metabolism; Medical sciences; Signal Transduction; Autoimmunity; Human; Immunopathology; Immune response; Pathogenesis; Cytokine; Autoimmune disease; Toll like receptor; Immune regulation; Effector; Immunology; Animal; Interferon
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/j.0105-2896.2005.00252.x

Interferons (IFNs) type‐1 (IFN α/β) and type‐II (IFN‐γ) are the most pleiotropic molecules in the intricate cytokine network. This dominance arises from three crucial factors: (i) initiation of IFN‐α/β and IFN‐γ production at the inception of most innate immune responses, which primes for the ensuing adaptive immune responses, primarily through the sine qua non upregulation of major histocompatibility complex and costimulatory molecules; (ii) magnification of their production and signaling by cross‐talk between themselves, and synergistic or antagonistic effects on other cytokines; and (iii) direct or indirect initiation of transcription of hundreds of immunologically relevant genes. Considering that aberrant immune responses against self‐molecules seem to depend on the same constituents and pathways as those against exogenous antigens, it follows that IFNs are also major effectors in the pathogenesis of autoimmunity. Here, we review the diverse biological effects of IFNs on the immune system, discuss findings pertaining to the nature of exogenous and endogenous stimuli that might induce IFN production through the engagement of Toll‐like receptors, and summarize the detrimental and, in some instances, beneficial effects of IFNs in systemic and organ‐specific autoimmune diseases.