RGD Reference Report - Novel role of aquaporin-4 in CD4+ CD25+ T regulatory cell development and severity of Parkinson's disease. - Rat Genome Database

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Novel role of aquaporin-4 in CD4+ CD25+ T regulatory cell development and severity of Parkinson's disease.

Authors: Chi, Y  Fan, Y  He, L  Liu, W  Wen, X  Zhou, S  Wang, X  Zhang, C  Kong, H  Sonoda, L  Tripathi, P  Li, CJ  Yu, MS  Su, C  Hu, G 
Citation: Chi Y, etal., Aging Cell. 2011 Jun;10(3):368-82. doi: 10.1111/j.1474-9726.2011.00677.x. Epub 2011 Mar 22.
RGD ID: 5148006
Pubmed: PMID:21255222   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1474-9726.2011.00677.x   (Journal Full-text)

Aquaporin-4 (AQP4) is highly expressed in mammalian brains and is involved in the pathophysiology of cerebral disorders, including stroke, tumors, infections, hydrocephalus, epilepsy, and traumatic brain injury. We found that AQP4-deficient mice were hypersensitive to stimulations such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or lipopolysaccharide compared to wild-type (WT) littermates. In a mouse model of MPTP-induced Parkinson's disease (PD), AQP4-deficient animals show more robust microglial inflammatory responses and more severe loss of dopaminergic neurons (DNs) compared with WT mice. However, a few studies have investigated the association of abnormal AQP4 levels with immune dysfunction. Here, for the first time, we report AQP4 expression in mouse thymus, spleen, and lymph nodes. Furthermore, the significantly lower numbers of CD4(+) CD25(+) regulatory T cells in AQP4-deficient mice compared to WT mice, perhaps resulting from impaired thymic generation, may be responsible for the uncontrolled microglial inflammatory responses and subsequent severe loss of DNs in the substantia nigra pars compacta in the MPTP-induced PD model. These novel findings suggest that AQP4 deficiency may disrupt immunosuppressive regulators, resulting in hyperactive immune responses and potentially contributing to the increased severity of PD or other immune-associated diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AQP4HumanParkinsonism severityISOAqp4 (Mus musculus) RGD 
Aqp4RatParkinsonism severityISOAqp4 (Mus musculus) RGD 
Aqp4MouseParkinsonism severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aqp4  (aquaporin 4)

Genes (Mus musculus)
Aqp4  (aquaporin 4)

Genes (Homo sapiens)
AQP4  (aquaporin 4)


Additional Information