Interferons (IFNs)

How do Interferons Become Activated?:

IFNs are a family of proteins that are produced by cells in response to viral infection or stimulation with double-stranded RNA, antigens, or mitogens. Anitviral type I interferons (IFN-beta and alpha) are induced by TLR3, 4, 7, 8 and 9.

What do Inteferons do?:

By virtue of their ability to compete for binding to a common type I receptor, IFNα and IFNβ are classified as type I IFNs whereas IFNγ binds to a distinct type II IFN receptor. Binding of IFNs to their receptors intiates signals that are transmitted from the cell surface to the nucleus and culminate in the rapid induction of a number of IFN-stimulated genes (ISGs). Gene products regulated by IFNs are the primary effectors of the IFN mediated biological responses. Alterations in gene expression result in modulation of receptors for other cytokines, concentration of regulatory proteins on the surface of immune effector cells and activation of enzymes that modulate cellular growth and function. IFNs are known to have the following effects:

• IFNs can interfere with subsequent viral challenge
• immunomodulatory effects
• Anti-tumor and antiproliferative effects: IFNs may elicit anti-tumor effects either by acting on tumor cells or on other cells. IFNs are considered as apoptosis inducing cytokines. Since 1996, cytotoxic function has been attributed to DCs caused by death ligands synthesized by DCs.
• Type I interferons promote the proliferation of memory T cells and prevent T cell apoptosis. Type I interferons can also activate STAT4 directly and induce IFNy secretion from CD8+ T cells in mice and CD4+ T cells in humans.

Type I Interferons:

Type II Interferons:

Type II interferon gamma is produced by T cells (CD8 & CD4) and NK cells and results in increased class I expression, activation of T, B neutrophils and NK cells.

IFNપ is secreted mainly by Th-1 lymphocytes and NK cells and is coded by a single gene on chromosome 12. Click here for more information on IFN-gamma.

IFN Signal Transduction:

Following secretion from cells, IFNs mediate their effects by binding to cell surface receptors and activate members of the JAK kinase family. Activated JAK kinases phosphorylate the signal transducers and activators of stranscription (STAT) family of transcription factors. STAT proteins homo-or heterodimerize and form complexes (GAF; ISGF3) with other transcription factors to activate transcription of IFN-stimulated genes (ISGs).