Anti-proliferative Activity of T-bet
| Autor: | Ji Hyun Shin, Yeon Ji Oh, Eun Sook Hwang, Hee Yeon Won |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Ecdysone
Proliferation Immunology Population Cell chemical and pharmacologic phenomena T-bet Precursor cell Th cells medicine Immunology and Allergy education IFN-γ Transcription factor education.field_of_study CD40 biology Cell growth IL-2 HEK 293 cells hemic and immune systems Embryonic stem cell Cell biology Infectious Diseases medicine.anatomical_structure biology.protein Original Article |
| Zdroj: | Immune Network |
| ISSN: | 2092-6685 1598-2629 |
| DOI: | 10.4110/in.2015.15.4.199 |
| Popis: | T-bet is a critical transcription factor that regulates differentiation of Th1 cells from CD4(+) precursor cells. Since T-bet directly binds to the promoter of the IFN-γ gene and activates its transcription, T-bet deficiency impairs IFN-γ production in Th1 cells. Interestingly, T-bet-deficient Th cells also display substantially augmented the production of IL-2, a T cell growth factor. Exogenous expression of T-bet in T-bet deficient Th cells rescued the IFN-γ production and suppressed IL-2 expression. IFN-γ and IL-2 reciprocally regulate Th cell proliferation following TCR stimulation. Therefore, we examined the effect of T-bet on Th cell proliferation and found that T-bet deficiency significantly enhanced Th cell proliferation under non-skewing, Th1-skewing, and Th2-skewing conditions. By using IFN-γ-null mice to eliminate the anti-proliferative effect of IFN-γ, T-bet deficiency still enhanced Th cell proliferation under both Th1- and Th2-skewing conditions. Since the anti-proliferative activity of T-bet may be influenced by IL-2 suppression in Th cells, we examined whether T-bet modulates IL-2-independent cell proliferation in a non-T cell population. We demonstrated that T-bet expression induced by ecdysone treatment in human embryonic kidney (HEK) cells increased IFN-γ promoter activity in a dose dependent manner, and sustained T-bet expression considerably decreased cell proliferation in HEK cells. Although the molecular mechanisms underlying anti-proliferative activity of T-bet remain to be elucidated, T-bet may directly suppress cell proliferation in an IFN-γ- or an IL-2-independent manner. |
| Databáze: | OpenAIRE |
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