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BOB.1/OBF.1 controls the balance of TH1 and TH2 immune responses
Author(s) -
Brunner Cornelia,
Sindrilaru Anca,
Girkontaite Irute,
Fischer KlausDieter,
Sunderkötter Cord,
Wirth Thomas
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601742
Subject(s) - biology , immune system , balance (ability) , immunology , neuroscience
BOB.1/OBF.1 is a transcriptional coactivator essential at several stages of B‐cell development. In T cells, BOB.1/OBF.1 expression is inducible by co‐stimulation. However, a defined role of BOB.1/OBF.1 for T‐cell function had not been discovered so far. Here, we show that BOB.1/OBF.1 is critical for T helper cell function. BOB.1/OBF.1 −/− mice showed imbalanced immune responses, resulting in increased susceptibility to Leishmania major infection. Functional analyses revealed specific defects in TH1 and TH2 cells. Whereas expression levels of TH1 cytokines were reduced, the secretion of TH2 cytokines was increased. BOB.1/OBF.1 directly contributes to the IFNγ and IL2 promoter activities. In contrast, increased TH2 cytokine production is controlled indirectly, probably via the transcription factor PU.1, the expression of which is regulated by BOB.1/OBF.1. Thus, BOB.1/OBF.1 regulates the balance of TH1 versus TH2 mediated immunity.