Abstract
Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19), an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits. IL-19 deficiency increased the production of such pro-inflammatory cytokines as IL-6 and tumor necrosis factor-α in activated microglia, and IL-19 treatment suppressed this effect. Moreover, in a mouse model of Alzheimer’s disease, we observed upregulation of IL-19 in affected areas in association with disease progression. Our findings demonstrate that IL-19 is an anti-inflammatory cytokine, produced by activated microglia, that acts negatively on microglia in an autocrine manner. Thus, microglia may self-limit their inflammatory response by producing the negative regulator IL-19.
Highlights
Microglia are the macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS)
These results indicate that IL-19 is predominantly produced by activated microglia in the CNS
We showed that activated microglia secrete IL-19 and are the only CNS cells to express functional IL-19 receptor
Summary
Microglia are the macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Their functions include antigen presentation to initiate the immunological reaction, direct attack against non-self antigens, debris clearance, and support of neuronal circuit development [1,2,3,4,5]. Abnormal activation of microglia often damages the CNS, and microglial activation is a characteristic pathological hallmark of various neurological disorders, including neuroinflammatory and neurodegenerative diseases [6,7,8,9,10,11,12]. Proinflammatory cytokines exacerbate neuroinflammation by fueling microglial activation, PLOS ONE | DOI:10.1371/journal.pone.0118640 March 20, 2015
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