Methods and compositions for modulating production of a T helper type 2 (Th2)-associated cytokine by regulating transcription factor activity in association with a Nuclear Factor of Activated T cells (NF-AT) protein

摘要

The specification describes methods for modulating production of a T helper type 2 (Th2)-associated cytokine, in particular interleukin-4, by modulating the activity of one or more transcription factors that cooperate with NF-AT family proteins to regulate expression of a Th2-associated cytokine gene. In one embodiment, the activity of a maf family protein (e.g., c-Maf or a small maf protein, such as p18) is modulated. In another embodiment, the activity of a protein that interacts with an NF-AT family protein (e.g., NIP45) is modulated. Combination methods, for example wherein the activities of a maf family protein and an NF-AT protein are modulated or the activities of a maf protein and an NF-AT-interacting protein are modulated, are also encompassed by the invention. Methods for modulating development of T helper type 1 (Th1) or T helper type 2 (Th2) subsets in a subject using agents that modulate transcription factor activity are also disclosed. NIP45 compositions, including isolated nucleic acid molecules encoding NIP45, antisense nucleic acid molecules, recombinant expression vectors containing a NIP45 nucleic acid molecule, host cells into which such expression vectors have been introduced and non-human transgenic animals carrying a NIP45 transgene, are also provided by the invention. The specification further provides isolated NIP45 proteins and peptides, NIP45 fusion proteins and anti-NIP45 antibodies. Methods of using the NIP45 compositions of the invention are also disclosed.