Expression of TRIM Genes in Different Immune Cells and Mechanism of Regulation of Their Expression: Implications for the Immune Response to Pathogens

The tripartite motif (TRIM) proteins are important in a variety of cellular functions including antiviral activity. We systematically analyzed mRNA expression of representative TRIMs in primary mouse macrophages, myeloid and plasmacytoid dendritic cells, and a selection of CD4+ T cell subsets. These cells have different effector functions in innate and adaptive immune responses, to a large extent due to the different patterns of cytokines that they produce. Here, we defined four clusters of TRIM genes based on their selective expression in these cell subsets. The first group of TRIMs was preferentially expressed in CD4+T cells and contained the COS-FN3 motif. Additional TRIMs were identified that showed up-regulation in macrophages and dendritic cells upon influenza virus infection in a type-I IFN dependent manner suggesting that they may play a role in anti-viral responses. However, stimulation of macrophages and mDC with LPS and double stranded RNA also led to type-I IFN dependent up-regulation of these TRIM genes, suggesting that their expression is not directly regulated by the virus, and that they may have broader functions in innate immune responses. In support of the proposed role of TRIMs in anti-viral responses, a subset of the type-I IFN dependent TRIMs mapped to mouse chromosome 7, syntenic to human chromosome 11 where TRIMs such as TRIM5, shown to have anti-viral activity, are localized. Consistent with these findings, up-regulation of the same TRIM genes in human macrophages was mainly observed under conditions which resulted in the induction of IFNβ (in this case by LPS and IFNγ stimulations), as observed by reanalysis of a previously published microarray study. Within the group of TRIMs induced by viruses in macrophages and dendritic cells via a type-I IFN dependent mechanism we distinguish two clusters on the basis of TRIM expression in CD4+ T cells. A fourth group of TRIMs was constitutively expressed in plasmacytoid dendritic cells independently of viral infection or signalling through the type-I IFN receptor. Our findings on expression and regulation of TRIMs may help to develop potential strategies for determining functions of this diverse family of molecules in immune cells