Figure 1.

Overall role of polyamines in inflammatory processes of immune subsets. Sparked by three high-impact publications, the role of polyamine on CD4+ T-cell physiology is highly controversial (A). In the first publication, (i) blockade of polyamine synthesis led to unstable lineage fidelity, resulting in uncontrolled inflammation. In the other publications, (ii) polyamine blockade led to the amelioration of experimental autoimmune encephalomyelitis (EAE) by preventing inflammatory Th17 pathogenesis and inducing a regulatory T-cell phenotype. In the only study to date that directly examines polyamine function in CD8+ T-cells, the authors found thorough CRISPR screening that the deletion of ODC1 led to enhanced cytotoxicity and the degranulation of T-cells (B). In myeloid lineage, cells and microglia polyamines are uniformly associated with inhibition of inflammation and autoimmune phenotypes (C). In dendritic cells (DCs), a metabolic positive feedforward loop instigated by IFN-y and/or TGF-b results in a tolerogenic phenotype (D). Blockade of many aspects of this pathway in DCs leads to increased autoimmune inflammation. Figure created with BioRender.com.