Distinct requirements for the naturally occurring splice forms Stat4  and Stat4  in IL-12 responses

• Published in: The EMBO journal 2003-08, Vol.22 (16), p.4237-4248
• Main Author: Hoey, T.
• Format: Article
• Language: English
• Subjects: Amino acids
• ISSN: 1460-2075; 0261-4189; 1460-2075
• DOI: 10.1093/emboj/cdg393

Signal transducer and activator of transcription (Stat)4 is a signaling molecule required for normal responses to interleukin-12 (IL-12) and is critically involved in inflammatory responses. We have isolated an alternatively spliced isoform of Stat4, termed Stat4[beta], which lacks 44 amino acids at the C-terminus, encompassing the putative transcriptional activation domain. To assess the in vivo roles of these Stat4 isoforms, we generated transgenic Stat4-deficient mice expressing Stat4[alpha] or Stat4[beta]. Our results indicate that T-cell-specific expression of Stat4[alpha] or Stat4[beta] can mediate many aspects of IL-12 signaling including the differentiation of Th1 cells. However, Stat4[alpha] is required for normal levels of IL-12-induced interferon-[gamma] production from Th1 cells. Microarray analysis identified 98 genes induced by both Stat4 isoforms, 32 genes induced only by Stat4[alpha] and 29 genes induced only by Stat4[beta]. Some induced genes correlate with specific functions including the ability of Stat4[beta], but not Stat4[alpha], to mediate IL-12-stimulated proliferation. Thus, Stat4[alpha] and Stat4[beta] have distinct roles in mediating responses to IL-12.