T helper differentiation proceeds through Stat1-dependent, Stat4- dependent and Stat4-independent phases

K. M. Murphy, W. Ouyang, S. J. Szabo, N. G. Jacobson, M. L. Guler, J. D. Gorham, U. Gubler, T. L. Murphy

Research output: Contribution to journalReview article

68 Scopus citations

Abstract

Much of our focus in understanding Th1/Th2 development has been on the signals delivered by IL-12 and IL-4 as final determinants of terminal T cell differentiation. Because extinction of IL-12 signaling in early Th2 development could potentially be important in imprinting a more permanent Th2 phenotype on a population of T cells, we have also examined various parameters regulating the IL-12 signaling pathway. Whereas IL-4 appears to repress functional IL-12 signaling through inhibition of IL-12R β2 expression, IFN-γ in the mouse, and IFN-α in the human appear to induce IL- 12R β2 expression and promote IL-12 responsiveness. We propose that Th1 development can be considered in two stages, capacitance and development. Capacitance would simply involve expression of IL-12R β1 and β2 subunits, regulated by TCR, IL-4 and IFNs. The second stage, development, we propose is the true IL-12 induced developmental stage, involving expression of Stat4 inducible proteins. In the human, this may also occur via IFN-α, which is able to activate Stat4. It is perhaps possible that all of Stat4 actions on Th1 development may be exert directly by Stat4 at the IFN-γ gene, however we suggest that, more likely, Stat4 may act to induce Th1 development through the induction of other non-cytokine genes, whose stable expression maintains the transcriptional state of a Th1 cell.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
JournalCurrent topics in microbiology and immunology
Volume238
StatePublished - Jan 11 1999

Fingerprint Dive into the research topics of 'T helper differentiation proceeds through Stat1-dependent, Stat4- dependent and Stat4-independent phases'. Together they form a unique fingerprint.

  • Cite this