An essential role for Rxr alpha in the development of Th2 responses.
A viable hypomorphic allele of mouse retinoid X receptor alpha (Rxralpha) was created by random germline mutagenesis. The mutation (I273N) alters the ligand binding and heterodimerization domain, and causes a 90% decline in ligand-inducible transactivation. Homozygotes develop progressive alopecia and dermal cysts, and progressive exaggeration of Th1 and loss of Th2 responses to antigen. Th1 skewing is directly caused by aberrant function of both antigen-presenting cells and naïve CD4 T cells; the predominant Th1 response to antigen is attributable to decreased suppression of regulatory T cells in mutant mouse. Dietary depletion of vitamin A in Th2-prone wild-type mice mimics the immune phenotype caused by the mutation. Hence, RXRalpha plays an important post-developmental role in the regulation of adaptive immune responses, and provides a plausible link between nutritional environment and the type of adaptive response that results from immunization.
Du
Xin
X
Department of Immunology, the Scripps Research Institute, La Jolla, CA 92037, USA.
Tabeta
Koichi
K
Mann
Navjiwan
N
Crozat
Karine
K
Mudd
Suzanne
S
Beutler
Bruce
B
D000375:Aging / Q000235:genetics / Q000276:immunology; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D047490:Retinoid X Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
D000534:Alum Compounds; D047490:Retinoid X Receptor alpha; C041524:aluminum sulfate; D010047:Ovalbumin