Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4

Nils G. Jacobson, Susanne J. Szabo, Renate M. Weber-Nordt, Zhong Zhong, Robert D. Schreiber, James E. Darnell, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

571 Scopus citations

Abstract

Interleukin 12 (IL-12) initiates the differentiation of naive CD4+ T cells to T helper type 1 (Th1) cells critical for resistance to intracellular pathogens such as Leishmania major. To explore the basis of IL-12 action, we analyzed induction of nuclear factors in Th1 cells. IL-12 selectively induced nuclear DNA-binding complexes that contained Stat3 and Stat4, recently cloned members of the family of signal transducers and activators of transcription (STATs). While Stat3 participates in signaling for several other cytokines, Stat4 was not previously known to participate in the signaling pathway for any natural ligand. The selective activation of Stat4 provides a basis for unique actions of IL-12 on Th1 development. Thus, this study presents the first identification of the early events in IL-12 signaling in T cells and of ligand activation of Stat4.

Original languageEnglish
Pages (from-to)1755-1762
Number of pages8
JournalJournal of Experimental Medicine
Volume181
Issue number5
DOIs
StatePublished - May 1 1995

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