Cytokine-mediated signalling and early defects in lymphoid development.
OBJECTIVE
The aim of the review is to report on recent advances in cytokine-mediated signalling, as illustrated by the study of natural human mutants. In particular, the role of cytokines and cytokine-mediated signalling in human T-cell development is analysed in detail, and currently available forms of treatment including experimental trials are described.


RESULTS
Defects of the cytokine/JAK/STAT axis have been recently described as responsible for human Severe Combined Immune Deficiency. In particular, defects in gammac, JAK3 and IL7RA have been analysed in terms of development of novel diagnostic tools as well as of new therapeutic agents for the treatment of autoimmune diseases and graft-versus-host disease.


CONCLUSIONS
Dissection of the genetic defects underlying the various forms of Severe Combined Immune Deficiency has helped develop new and more accurate diagnostic assays and novel forms of treatment.
Giliani
Silvia
S
Angelo Nocivelli Institute of Molecular Medicine and Department of Pediatrics, University of Brescia, Brescia, Italy. giliani@master.cci.unibs.it
Mella
Patrizia
P
Savoldi
Gianfranco
G
Mazzolari
Evelina
E
D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D053616:Janus Kinase 3; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics*
D016207:Cytokines; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D020395:Receptors, Interleukin-7; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3