Congenital defects in the interferon-gamma/interleukin-12 pathway.
OBJECTIVE
The aim of this review is to highlight the most recent and relevant advances in the interferon-gamma/interleukin-12 pathway, a pivotal player of the immune system, and their repercussions on basic and clinical aspects of science.


RESULTS
Newly described mutations are helping us to dissect the interferon-gamma/interleukin-12 pathway and its role in genetic infectious susceptibility and autoimmunity, and to reevaluate the pathophysiologic mechanisms involved in dominant and recessively inherited mutations.


CONCLUSIONS
The interferon-gamma/interleukin-12 pathway plays a central role in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the interferon-gamma/interleukin-12 pathway is also involved in the pathogenesis of autoimmune disease, as well as tumor development and control. Genotype-phenotype correlations have been established for certain mutants in this pathway, some of which have therapeutic implications.
Rosenzweig
Sergio D
SD
Division of Immunology, Department of Pediatrics, Hospital Nacional de Pediatría Juan P. Garrahan, Buenos Aires, Argentina.
Holland
Steven M
SM
D000013:Congenital Abnormalities / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000172:deficiency; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D009154:Mutation; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency
D004268:DNA-Binding Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma