Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Nov 24;13(1):297.
doi: 10.1186/s12974-016-0763-8.

Balancing the Immune Response in the Brain: IL-10 and Its Regulation

Affiliations
Free PMC article
Review

Balancing the Immune Response in the Brain: IL-10 and Its Regulation

Diogo Lobo-Silva et al. J Neuroinflammation. .
Free PMC article

Abstract

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology.

Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders.

Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.

Keywords: Glial cells; Interleukin-10; Molecular regulation; Neurodegeneration; Pattern recognition receptors.

Figures

Fig. 1
Fig. 1
The role of IL-10 receptor signalling in anti-inflammation. Overview of the IL-10R signalling cascade and the main cellular effects triggered by IL-10
Fig. 2
Fig. 2
Molecular mechanisms regulating IL-10 production in microglia and astrocytes. Signalling cascades, transcription factors and miRNAs involved in regulating the production of IL-10 in TLR-triggered microglia or astrocytes. Grey arrows indicate positive signals; red lines indicate IL-10 silencing pathways. Also indicated are known enhancers and blockers of IL-10 production

Similar articles

See all similar articles

Cited by 59 articles

See all "Cited by" articles

References

    1. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081–2095. doi: 10.1084/jem.170.6.2081. - DOI - PMC - PubMed
    1. O'Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol. 2007;7:425–428. doi: 10.1038/nri2097. - DOI - PubMed
    1. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–274. doi: 10.1016/0092-8674(93)80068-P. - DOI - PubMed
    1. Engelhardt KR, Grimbacher B. IL-10 in humans: lessons from the gut, IL-10/IL-10 receptor deficiencies, and IL-10 polymorphisms. Curr Top Microbiol Immunol. 2014;380:1–18. - PubMed
    1. Dennis KL, Blatner NR, Gounari F, Khazaie K. Current status of interleukin-10 and regulatory T-cells in cancer. Curr Opin Oncol. 2013;25:637–645. doi: 10.1097/CCO.0000000000000006. - DOI - PMC - PubMed

Publication types

Feedback