BOB.1/OBF.1 controls the balance of TH1 and TH2 immune responses.
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 IFNgamma 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.
Brunner
Cornelia
C
Institute of Physiological Chemistry, University of Ulm, Ulm, Germany.
Sindrilaru
Anca
A
Girkontaite
Irute
I
Fischer
Klaus-Dieter
KD
Sunderkötter
Cord
C
Wirth
Thomas
T
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C490424:Pou2af1 protein, mouse