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PLoS One ; 6(4): e18498, 2011 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-21533228

RESUMO

BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2(+) lymphocytes resulted in a severe reduction of CD4(+)CD8(+) (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.


Assuntos
Linfócitos B/citologia , Proteína 2 de Resposta de Crescimento Precoce/fisiologia , Linfócitos T/citologia , Animais , Apoptose , Linfócitos B/metabolismo , Sequência de Bases , Primers do DNA , Proteína 2 de Resposta de Crescimento Precoce/genética , Citometria de Fluxo , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Transgênicos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Receptor Notch1/metabolismo , Linfócitos T/metabolismo , Timo/citologia , Timo/metabolismo
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