IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

Abstract : Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin. Cytokines are a class of signaling molecules expressed by many cell types, and especially those of the immune system. They are classified in seven major families: the type I cytokine, the type II cytokine (1), the IL-1 (2), and the TGF-β (3) families, the TNF superfamily (4), the receptor tyrosine kinase cytokine family (5), and the chemokine family (6). Although exhibiting pleiotropic properties, they are pivotal regulators of innate and adaptive immune defenses, inflammation, and hematopoiesis. The term "interleukin" (IL) originally refers to a group of cytokines expressed by leukocytes. To date, interleukins have been reported expressed by a wide variety of immune and non-immune cells and exhibit a large panel of properties (e.g., affecting proliferation, activation, differentiation, maturation, migration, and adhesion). Although agonist/antagonist activities and redundancy make any classification particularly complicated, different classifications have been proposed based on their functions, receptor usage or structure. As an example, a functional classification distinguishes eight subgroups of interleukins (IL-1, common γ chain receptor cytokine, cytokines of type 2 immune responses, interleukins with chemokine activity, the IL-10, IL-12, and IL-17 families and, others) (7). A structure-based classification has been also proposed, dividing interleukins into four major groups: IL-1-like cytokines, class I helical cytokines (IL-4-, IL-6-, and IL-12-like ILs, common γ chain receptor cytokines), class II helical cytokines (IL-10-and IL-28-like molecules) and the IL17-like cytokines (8).
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Vincent Larochette, Charline Miot, Caroline Poli, Elodie Beaumont, Philippe Roingeard, et al.. IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense. Frontiers in Immunology, Frontiers, 2019, 10, ⟨10.3389/fimmu.2019.00204⟩. ⟨inserm-02055151⟩

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