Astrocyte‐targeted IL‐10 production decreases proliferation and induces a downregulation of activated microglia/macrophages after PPT. Issue 4 (11th December 2018)

• Record Type: Journal Article
• Authors: Recasens, Mireia; Shrivastava, Kalpana; Almolda, Beatriz; González, Berta; Castellano, Bernardo
• Is Part Of: Glia. Volume 67:Issue 4(2019)
• Page Start: 741
• Page End: 758
• Publication Date: 2018-12-11
• Subjects: cytokines -- flow cytometry -- IL‐10R -- macrophage infiltration -- T‐cell; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23573
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin‐10 (IL‐10) has been demonstrated after different types of CNS injuries and associated with protective functions, the specific role played by IL‐10 modulating microglial cells remains unclear. Hence, the objective of this study was to evaluate the effects of transgenic astrocyte IL‐10 production on microglial activation associated with axonal anterograde degeneration. To address it, the hippocampal area subjected to perforant pathway transection (PPT) was analyzed by immunohistochemistry (IHC), flow cytometry and protein microarray in transgenic (GFAP‐IL10Tg) mice and their corresponding wild types (WT) littermates. Our results demonstrated increased microglial/macrophages density in nonlesioned and PPT‐lesioned GFAP‐IL10Tg animals when compared with nonlesioned and lesioned WT, respectively. This increase was not due to proliferation, as GFAP‐IL10Tg mice showed a reduced proliferation of microglial cells, but was related to an increased population of CD11b+/CD45 high monocyte/macrophages. Despite this higher number, the microglia/macrophage population in transgenic animals displayed a downregulated phenotype characterized by lower MHCII, ICOSL, and CD11c. Moreover, a sustained T‐cell infiltration was found in transgenic animals. We strongly suggest these modifications must be associated with indirect effects derived from the influence of IL‐10 on astrocytes and/or neurons, which express IL‐10R. We finally suggested that TGF‐β produced by astrocytes, along with IL‐2 and CXCL10 might be crucial molecules mediating the effects of transgenic IL‐10. Main Points: Astrocyte‐targeted IL‐10 increases microglia/macrophage density but induced a down‐regulated activated phenotype after PPT. All these modifications must be an indirect effect derived from the influence of IL‐10 over astrocytes and neurons.