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EMBO J ; 30(13): 2690-704, 2011 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-21587207

RESUMO

Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α(+) and CD103(+) DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103(+) and CD8α(+) lineages. Notably, CD103(+) DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α(-) DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP(+) DCs. It did not restore cross-presenting capacity to Batf3(-/-) or CD103(-)Sirp-α(-)DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.


Assuntos
Antígenos CD/metabolismo , Antígenos CD8/metabolismo , Linhagem da Célula/genética , Células Dendríticas/fisiologia , Proteína 2 Inibidora de Diferenciação/genética , Cadeias alfa de Integrinas/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Células Dendríticas/metabolismo , Expressão Gênica/fisiologia , Genes cdc/fisiologia , Proteína 2 Inibidora de Diferenciação/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos
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