Expression of IL-10 in Th memory lymphocytes is conditional on IL-12 or IL-4, unless the IL-10 gene is imprinted by GATA-3.
Eur J Immunol
; 37(3): 807-17, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17304625
ABSTRACT
In Th1 and Th2 memory lymphocytes, the genes for the cytokines interleukin (IL)-4 and interferon-gamma (IFN-gamma) are imprinted for expression upon restimulation. This cytokine memory is based on expression of the transcription factors T-bet for IFN-gamma, and GATA-3 for IL-4, and epigenetic modification of the cytokine genes. In Th2 cells, expression of the cytokine IL-10 is also induced by GATA-3. Here, we show that this induction is initially not accompanied by epigenetic modification of the IL-10 gene. Only after repeated restimulation of a memory Th2 cell in the presence of IL-4, extensive histone acetylation of the IL-10 gene is detectable. This epigenetic imprinting correlates with the development of a memory for IL-10 in repeatedly restimulated Th2 cells. In Th1 cells, IL-10 expression is induced by IL-12, but the IL-10 gene lacks detectable histone acetylation. Accordingly, IL-10 expression in restimulated memory Th1 cells remains conditional on the presence of IL-12. This finding defines a potential anti-inflammatory role for IL-12 in Th1 recall responses. While in primary Th1 responses IL-12 is required to induce expression of the pro-inflammatory cytokine IFN-gamma, in secondary Th1 responses IFN-gamma re-expression is independent of IL-12, which still is able to induce expression of the anti-inflammatory cytokine IL-10.
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Banco de datos:
MEDLINE
Asunto principal:
Interleucina-4
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Interleucina-10
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Linfocitos T Colaboradores-Inductores
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Interleucina-12
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Impresión Genómica
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Factor de Transcripción GATA3
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Memoria Inmunológica
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania