Thenuclearreceptorsuperfamilyandthetranscriptionalfactorsassociatedwithcytokinesareinherentlydifferentfamiliesofsignalingmoleculesandactivategenetranscriptionbybindingtotheirrespectiveresponsiveelement.However,ithasbecomeincreasinglyclearfromourworksandothersthatnuclearreceptorsareimportantregulatorsofcytokineproductionandfunctionthroughcomplexandvariedinteractionsbetweenthesedistincttranscriptionalfactors.Thisreviewprovidesageneraloverviewofthemechanismofactionofnuclearreceptorsandtheirtranscriptionalcrosstalkwithtranscriptionalfactorsassociatedwithcytokinetransductionpathways.Oneofthemostimportantmechanisticaspectsisproteintoproteininteractionthroughadirectorco-regulator-mediatedindirectmanner.Suchcrosstalkiscruciallyinvolvedinphysiologicalandtherapeuticrolesofnuclearreceptorsandtheirligandsinimmunity,inflammationandcytokine-relatedtumors.Cellular&MolecularImmunology.2004;1(6):416-424.