Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases

Abstract

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection, cell stress, neuronal disease, and tumors. Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity. The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27, its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases. Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system. Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain. Interleukin-27 is secreted from and binds to infiltrating microglia, macrophage, astrocytes, and even neurons and it promotes neuronal survival by regulating pro- and anti-inflammatory cytokines, neuroinflammatory pathways, oxidative stress, apoptosis, autophagy, and epigenetic modifications. However, interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations. In this review, we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain, spinal cord, and retina. We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.

Adipose‐derived mesenchymal stem cells ameliorates experimental autoimmune encephalomyelitis via modulation of Th1/Th17 and expansion of Th2/Treg responses

“…Recently, two newly discovered cytokines namely, IL‐27 and IL‐33 have drawn great attention of researchers in the pathogenesis of MS. IL‐27, a novel heterodimeric cytokine belonging to the IL‐12 superfamily, is predominantly produced by the APCs which can exert either positive or negative regulatory effects upon immune responses (Xu et al, 2017). IL‐27 is of critical importance in the limitation of autoimmune diseases and CNS inflammation in several experimental models and it's the anti‐inflammatory effects of IL‐35 are not only manifested in the suppression of Th1 and T17 responses but also are characterized by the promotion of Treg cells (Mascanfroni et al, 2013; Nortey et al, 2022). Importantly, it has also been reported that mice that lack the receptor for IL‐27 or IL‐27‐downstream signaling transcription factors are highly linked to susceptibility to EAE (Fitzgerald, Ciric, et al, 2007; Peters et al, 2015), and continuous infusion and delivery of IL‐27 has been shown to ameliorate neuropathology in EAE (Casella et al, 2017; Fitzgerald, Zhang, et al, 2007).…”

GEO Data Sets Analysis On Mechanism of Action of IFNβ-1a Treatment in Multiple Sclerosis

“…Firstly, "interleukin-27-mediated signalling pathway" was enriched for > 100 folds. The role of interleukin-27 (IL-27) in regulating T cell responses that prevent immune hyperactivity has been extensively characterized and IL-27 has been investigated as a possible therapeutic for chronic inflammatory conditions with excessive T cell activation, which includes MS [22].…”

“…Firstly, “interleukin-27-mediated signalling pathway” was enriched for > 100 folds. The role of interleukin-27 (IL-27) in regulating T cell responses that prevent immune hyperactivity has been extensively characterized and IL-27 has been investigated as a possible therapeutic for chronic inflammatory conditions with excessive T cell activation, which includes MS [22]. On the other hand, the anti-inflammatory capability of IL-27 can also be induced from other cell types in the central nervous system such as macrophages, microglia, and dendritic cells [23].…”

Autoimmune Neuroinflammatory Diseases: Role of Interleukins

“…Inhibits neuroinflammation and promotes neuroprotection and repair by inhibiting the production of pro-inflammatory cytokines and promoting the differentiation of type 1 regulatory T cells [15] IL-35…”