Caloric restriction has been found to influence a wide variety of age- sensitive immunological parameters such as interleukin-2 (IL-2) gene expression. However, the molecular mechanism responsible for the increased IL-2 expression with caloric restriction has been studied to only a limited extent. IL-2 plays a critical role in immune function, and several studies indicate that the induction of Il-2 expression by mitogens is enhanced by dietary restriction. The focus of this proposal is to study the molecular mechanisms responsible for the increased expression of IL-22 by caloric restriction. Recent studies have shown that the transcription of IL-2 is under control of several transcription factors of which NFAT plays a primary role in t he regulation of Il-2 transcription in T cells. NFAT is consisted of a nuclear component and a cytoplasmic component, which is essential for IL-2 transcription. In this study, I propose the following hypothesis; The increase in IL-2 expression with dietary restriction arises from an alteration at the level of transcription that involves the transcription factor NFAT.
The specific aims of the proposal are; 1) to determine if the increase in IL-2 expression with dietary restriction is correlated to changes in the transcription of IL-2, 2) to determine if the increase in Il-2 transcription is correlated to changes in the T cell specific transcription factor, NFAT, and non-T cell specific transcription factors. 3) to determine if an alteration in the nuclear components of the NFAT complex are responsible for the increase in NFAT binding activity and il-2 transcription, and 4) to determine if the cytoplasmic component of the NFAT complex (NFAT-c) is responsible for the increase in NFAT binding activity and Il-2 transcription.
