Developmentally regulated gene expression of Th2 cytokines in the brain.
Given the critical role of cytokines in the regulation of an inflammatory response, we investigated whether certain cytokines are expressed in the brains of normal mice during maturation that could contribute to the immune-privileged nature of the CNS or potentially influence an immune-mediated illness such as experimental allergic encephalomyelitis. The gene expression of IFN gamma (Th1 cytokine) and IL-4 (Th2 cytokine) was analyzed in the brain of several strains of mice. IFN gamma was not detectable. However, IL-4 was present in the brains of neonatal mice, but not adult mice. Resident CNS cells are believed to be the source of the IL-4, because mice deficient in T cells (SCID and RAG2-/-) expressed the IL-4 gene in the CNS. Further analysis indicated that the gene expression of the Th2 cytokine transcription factor, GATA-3, correlated with IL-4 and IL-10 expression in the brain. Since GATA-3-deficient mice have an abnormal CNS, brain-derived Th2 cytokines may play an important role in CNS development, as well as potentially contribute to the immune-privileged nature of the brain.
Lovett-Racke
A E
AE
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. alovet@mednet.swmed.edu
Smith
M E
ME
Arredondo
L R
LR
Bittner
P S
PS
Ratts
R B
RB
Shive
C L
CL
Forsthuber
T G
TG
Racke
M K
MK
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000276:immunology; D001923:Brain Chemistry / Q000235:genetics* / Q000276:immunology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma