PPARgamma, a lipid-activated transcription factor as a regulator of dendritic cell function

Abstract

In recent years it became apparent that PPARgamma, besides being a key component of adipose tissue development and a target of insulin-sensitizing drugs, also has a role in immune cell differentiation and function. This receptor has been identified by us and others as a conductor of lipid handling in macrophages, and has roles also in inflammation control. Here we review recent advances on the role of this nuclear receptor in another key cell type of myeloid origin, dendritic cells (DCs). DCs are professional antigen-presenting cells having essential roles in antigen-uptake processing and presentation and in initiation of various forms of immune responses. It appears that PPARgamma is expressed and is active in myeloid DCs and likely to be a regulator of DC function by altering antigen uptake, maturation, activation, migration, cytokine production, and lipid antigen presentation. Thus PPARgamma is at the crossroads of lipid metabolism and innate immune response, and by studying its functions one has a unique opportunity to discern how these two seemingly distant fields (lipid metabolism and immune response) are interrelated. It is also possible that this receptor is a relevant target for pharmacological intervention in immune diseases such as chronic inflammation and autoimmune conditions.