ABSTRACT
Interferon-g (IFN-g; gene symbol IFNG) is a key modulator of innate and adaptive immune responses and is therefore involved in host protection against viral, bacterial and parasitic infections. The cytokine is known to polarize the acquired immune response toward a Th1 profile (see Chapter 1 for review of the biology of IFN-g). A variety of IFNG or IFNGR gene targeting models have been utilized in attempts to define the multifaceted, and often seemingly contradictory (i.e. disease-promoting or -limiting) effects of this cytokine in autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), diabetes, lupus and inflammatory bowel disease (IBD). Equally, systemic administration of IFN-g or IFN-g-antagonists in experimental animal models pronouncedly affects predisposition to, or recovery from, autoimmune conditions or fungal, bacterial, helminth, or protozoal infections. IFNG has been mapped to human chromosome 12q15, a region showing linkage to MS, RA, IBD, asthma and Type I and II diabetes in a number of genome-wide screens (summarized in Ref. 1). Thus, it is precisely such positional evidence, in combination with the finding of IFN-g being crucially involved in phenotypic expression or modulation of so wide an array of multifactorial conditions, that has made IFNG a prime target of numerous candidate gene studies on complex diseases and conditions.
