Role of the transcriptional repressor BCL6 in allergic response and inflammation 英文参考文献.docVIP

REVIEWARTICLE RoleoftheTranscriptionalRepressorBCL6in AllergicResponseandInflammation MasafumiArima,*TakeshiFukuda,TandTakeshiTokuhisa* Various allergy-related molecules are basically con- Abstract: Various molecules participate in different phases of allergic reactions. This means that many genes are encoding molecules related to allergic reactions, such as cytokines, chemo- kines,andtheir receptorsaseffectormolecules.Thetranscriptional repressor BCL6 has emerged as a multifunctional regulator of lymphocyte differentiation and immune responses. BCL6-de?cient (BCL6j/j)micedisplayThelpertype2(Th2)Ytypein?ammation, which is caused by abnormality of both lymphoid cells and nonlymphoid cells. Thus, BCL6 apparently contributes to negative regulation of various central molecules such as cytokines, in particular Th2 cytokines, CC chemokines, and immunoglobulin E inallergicdiseases.Therefore,BCL6maybeamoleculartargetfor Th2-typeallergicdiseases. trolled by transcriptional regulators, critical molecules believed to govern the pathogenesis of allergic diseases by regulating cytokine production, mediator synthesis, and IgE production at gene expression levels. Recent genetic studies havedemonstrated that transcriptional factors andregulators are involved in the development of allergic diseases. The molecular mechanisms of allergic diseases, in particular bronchial asthma, are gradually becoming clearer. However, nearly all previous studies of transcriptional factors have focusedonactiveregulators,includingGATAbindingprotein 3(GATA3),signaltransducerandactivatoroftranscription6 (STAT6), c-Maf, NF-AT, NF-JB, and c-fos. The functional rolesoftranscriptionalrepressorsinallergicdiseasesremain poorly understood. Because transcriptional repressors may have an important role in tuning physiologically optimal transcription,functionalfailureoftightlycontrolledconstitu- tivemechanismsregulatedbyagivenrepressormayleadtothe developmentofallergicdiseases. KeyWords:allergy,BCL6,cytok