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Splice variants of human FOXP3 are functional inhibitors of human CD4 + T‐cell activation
Author(s) -
Smith Emma L.,
Finney Helene M.,
Nesbitt Andrew M.,
Ramsdell Fred,
Robinson Martyn K.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02425.x
Subject(s) - foxp3 , exon , splice , t cell , alternative splicing , biology , il 2 receptor , gene , microbiology and biotechnology , population , repressor , genetics , mutation , splice site mutation , gene isoform , regulatory t cell , immune system , gene expression , medicine , environmental health
Summary FOXP3 has been identified as a key regulator of immune homeostasis. Mutations within the FOXP3 gene result in dysregulated CD4 + T‐cell function and elevated cytokine production, leading to lymphoproliferative disease. FOXP3 expression in CD4 + T cells is primarily detected with the CD4 + CD25 + regulatory T‐cell population. In humans the protein is detected as a doublet following immunoblot analysis. The lower band of the doublet has been identified as a splice isoform lacking a region corresponding to exon 2. The aim of this study was to investigate whether the splice variant form lacking exon 2 and a new novel splice variant lacking both exons 2 and 7, were functional inhibitors of CD4 + T‐cell activation. The data generated showed that full‐length FOXP3 and both splice variant forms of the protein were functional repressors of CD4 + T‐cell activation.