RGD Reference Report - A gene-dosage effect for interleukin-4 receptor alpha-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis. - Rat Genome Database

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A gene-dosage effect for interleukin-4 receptor alpha-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis.

Authors: Muller, U  Stenzel, W  Kohler, G  Polte, T  Blessing, M  Mann, A  Piehler, D  Brombacher, F  Alber, G 
Citation: Muller U, etal., J Infect Dis. 2008 Dec 1;198(11):1714-21.
RGD ID: 4890005
Pubmed: (View Article at PubMed) PMID:18954266
DOI: Full-text: DOI:10.1086/593068

Interleukin (IL)-4 and IL-13 are key factors in the pathogenesis of bronchopulmonary mycosis induced in mice by infection with Cryptococcus neoformans. Both cytokines use the IL-4 receptor alpha-chain (IL-4Ralpha). In this study, we investigated the role played by IL-4Ralpha expression in susceptibility to pulmonary C. neoformans infection. IL-4Ralpha(-/-) mice were extremely resistant. To characterize the effect of IL-4Ralpha expression level on disease outcome, we generated IL-4Ralpha(+/-) first-generation (F1) mice. IL-4Ralpha(+/-) mice showed intermediate levels of IL-4Ralpha expression, in contrast to higher levels in wild-type mice and no expression in IL-4Ralpha(-/-) mice, indicating biallelic expression of the gene for IL-4Ralpha (Il4ra). Concomitant with intermediate IL-4Ralpha expression, F1 mice showed intermediate susceptibility associated with altered Th2/Th17 cytokine production, decreased immunoglobulin E levels, and reduced allergic inflammation. This indicates a gene-dosage effect of IL-4Ralpha expression on susceptibility to bronchopulmonary mycosis. These data provide the basis for novel therapies antagonizing IL-4Ralpha in Th2-related pulmonary infection and possibly also in asthma.



Disease Annotations    
cryptococcosis  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Il4r  (interleukin 4 receptor)

Genes (Mus musculus)
Il4ra  (interleukin 4 receptor, alpha)

Genes (Homo sapiens)
IL4R  (interleukin 4 receptor)


Additional Information