Polyamines and Kynurenines at the Intersection of Immune Modulation. Issue 11 (November 2020)

• Record Type: Journal Article
• Authors: Proietti, Elisa; Rossini, Sofia; Grohmann, Ursula; Mondanelli, Giada
• Is Part Of: Trends in immunology. Volume 41:Issue 11(2020)
• Page Start: 1037
• Page End: 1050
• Publication Date: 2020-11
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2020.09.007
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Polyamines (i.e., putrescine, spermidine, and spermine) are bioactive polycations capable of binding nucleic acids and proteins and modulating signaling pathways. Polyamine functions have been studied most extensively in tumors, where they can promote cell transformation and proliferation. Recently, spermidine was found to exert protective effects in an experimental model of multiple sclerosis (MS) and to confer immunoregulatory properties on dendritic cells (DCs), via the indoleamine 2, 3-dioxygenase 1 (IDO1) enzyme. IDO1 converts l -tryptophan into metabolites, collectively known as kynurenines, endowed with several immunoregulatory effects via activation of the arylhydrocarbon receptor (AhR). Because AhR activation increases polyamine production, the emerging scenario has identified polyamines and kynurenines as actors of an immunoregulatory circuitry with potential implications for immunotherapy in autoimmune diseases and cancer. Highlights: Polyamines (i.e., putrescine, spermidine, and spermine) are bioactive polycations derived from the decarboxylation of ʟ-ornithine catalyzed by ornithine decarboxylase (ODC). Emerging data suggest that spermidine exerts anti-inflammatory/immunoregulatory effects; it can protect mice from experimental autoimmune encephalomyelitis and imiquimod-induced psoriasis. Kynurenines are carboxylated products derived from the oxidative cleavage of the essential amino acid tryptophan, mediated by indoleamine 2, 3-dioxygenase 1 (IDO1). Kynurenines are endowed with several immunoregulatory effects via the activation of the arylhydrocarbon receptor (AhR). Polyamines and kynurenines are emerging players in immunoregulatory networks involving AhR that could be considered in immunotherapy approaches to treat certain autoimmune diseases and cancers.