Sustained IL-12 signaling is required for XXXX development.

@entity1 @entity1198 @entity7116 @entity1199 @entity3027
@entity7116 is an essential transcription factor for @entity1198 cell development. IL-12 and @entity3027 both activate @entity7116 , but with different kinetics. In this study we compared their capacities to drive differentiation of @entity1 naive Th cells toward the @entity1198 phenotype. The @entity1198 -polarizing activity of @entity3027 was much weaker than that of IL-12, correlating with a marked difference in the kinetics of @entity7116 activation; the response to IL-12 was sustained (>48 h), whereas the response to @entity3027 was transient (4 h). The continuous presence of IL-12 was required for sustained @entity7116 activation. Similarly, optimal @entity1198 polarization was only achieved upon prolonged exposure to IL-12 and could not be induced by a transient IL-12 pulse. Furthermore, the cytokine @entity1199 potentiated sustained IL-12/ @entity7116 responses through up-regulation of IL-12R expression and synergized with IL-12 in driving @entity1198 cell development. Transient @entity3027 responses, on the other hand, were not prolonged by @entity1199 . @entity3027 treatment induced down-regulation of IFN-alphabeta receptor subunit 1, rendering cells refractory to @entity3027 , but did not trans-inhibit the IL-12/ @entity7116 response. These data indicate that sustained IL-12 signaling is essential for optimal @entity1198 cell development and that transient activation of @entity7116 in response to @entity3027 may explain the poor @entity1198 -polarizing capacity of this cytokine. Collectively these data show that the duration of cytokine signaling is important for determining the biological response.
