IL-7 plays a central role in regulating the growth and differentiation
of T cells. We have reported previously that epidermal keratinocytes
produce biologically relevant amounts of IL-7, thereby supporting the
growth of epidermal gamma delta T cells. In this report, we report tha
t IL-7 gene expression is regulated in keratinocytes by IFN-gamma. Tre
atment of Pam 212 keratinocytes with IFN-gamma induced a preferential
expression of 2.6- and 1.5-kb IL-7 mRNAs, in addition to the 2.9- and
1.7-kb mRNAs that are expressed constitutively. The 2.6- and 1.5-kb mR
NAs are produced through the use of alternative transcription initiati
on sites; these mRNAs are transcribed within 250 bp from the coding se
quence, whereas 2.9- and 1.7-kb mRNAs contain >400 bases in the 5'-unt
ranslated region. IFN-gamma appears to promote this conversion through
the IFN-stimulated response element (ISRE), which is located 270 bp u
pstream from the coding sequence. ISRE is followed by the initiator, a
non-TATA-type transcription control element. Functional relevance of
the ISRE/initiator complex was suggested by the observations that IFN-
gamma-dependent transcription was initiated from immediately downstrea
m of this complex, and that its deletion resulted in an abrogated IFN-
gamma responsiveness in transcriptional regulation. These results docu
ment a novel mechanism by which IL-7 gene expression is regulated in k
eratinocytes by a cytokine produced by T cells (IFN-gamma).