ROG negatively regulates T-cell activation but is dispensable for Th-cell differentiation.
ROG, a transcriptional repressor, is a direct target gene of NF-AT and a putative negative regulator of T-cell activation. In addition, overexpression of ROG suppresses the activity of GATA-3, implying a role of ROG in the differentiation and function of Th cells. Despite these observations, the function of ROG has yet to be confirmed by loss-of-function approaches. Here we report that ROG-deficient T cells are hypersensitive to anti-CD3 stimulation and produce more interleukin-2 (IL-2) due to enhanced NF-kappaB activity. ROG-deficient dendritic cells also produce more IL-12p40, another NF-kappaB target gene. However, ROG-deficient Th cells are capable of differentiating into Th1 and Th2 cells, and ROG-deficient mice have no defect in mounting appropriate Th immune responses in vivo. Thus, ROG is dispensable for the differentiation and function of Th cells but serves as a mediator of NF-AT-initiated suppression of NF-kappaB. Its mechanism of action and its expression pattern are distinct from those of other transcription factors negatively regulating the activation of T cells.
Kang
Bok Yun
BY
Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women's HospitalSmith Building, Room 524, One Jimmy Fund Way, Boston, MA 02115, USA.
Miaw
Shi-Chuen
SC
Ho
I-Cheng
IC
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053762:Interleukin-12 Subunit p40; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*
D017252:CD3 Complex; D053762:Interleukin-12 Subunit p40; D016328:NF-kappa B; D021122:Protein Subunits; D012097:Repressor Proteins; C406863:Rog protein, mouse; D018664:Interleukin-12