Sénécal, V;
Deblois, G;
Beauseigle, D;
Schneider, R;
Brandenburg, J;
Newcombe, J;
Moore, CS;
... Arbour, N; + view all
(2016)
Production of IL-27 in multiple sclerosis lesions by astrocytes and myeloid cells: Modulation of local immune responses.
Glia
, 64
(4)
pp. 553-569.
10.1002/glia.22948.
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Abstract
The mechanisms whereby human glial cells modulate local immune responses are not fully understood. Interleukin-27 (IL-27), a pleiotropic cytokine, has been shown to dampen the severity of experimental autoimmune encephalomyelitis, but it is still unresolved whether IL-27 plays a role in the human disease multiple sclerosis (MS). IL-27 contribution to local modulation of immune responses in the brain of MS patients was investigated. The expression of IL-27 subunits (EBI3 and p28) and its cognate receptor IL-27R (the gp130 and TCCR chains) was elevated within post-mortem MS brain lesions compared with normal control brains. Moreover, astrocytes (GFAP(+) cells) as well as microglia and macrophages (Iba1(+) cells) were important sources of IL-27. Brain-infiltrating CD4 and CD8 T lymphocytes expressed the IL-27R specific chain (TCCR) implying that these cells could respond to local IL-27 sources. In primary cultures of human astrocytes inflammatory cytokines increased IL-27 production, whereas myeloid cell inflammatory M1 polarization and inflammatory cytokines enhanced IL-27 expression in microglia and macrophages. Astrocytes in postmortem tissues and in vitro expressed IL-27R. Moreover, IL-27 triggered the phosphorylation of the transcription regulator STAT1, but not STAT3 in human astrocytes; indeed IL-27 up-regulated MHC class I expression on astrocytes in a STAT1-dependent manner. These findings demonstrated that IL-27 and its receptor were elevated in MS lesions and that local IL-27 can modulate immune properties of astrocytes and infiltrating immune cells. Thus, therapeutic strategies targeting IL-27 may influence not only peripheral but also local inflammatory responses within the brain of MS patients.
| Type: | Article |
|---|---|
| Title: | Production of IL-27 in multiple sclerosis lesions by astrocytes and myeloid cells: Modulation of local immune responses |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/glia.22948 |
| Publisher version: | http://dx.doi.org/10.1002/glia.22948 |
| Language: | English |
| Additional information: | This is the peer reviewed version of the following article: Sénécal, V; Deblois, G; Beauseigle, D; Schneider, R; Brandenburg, J; Newcombe, J; Moore, CS; (2016) Production of IL-27 in multiple sclerosis lesions by astrocytes and myeloid cells: Modulation of local immune responses. Glia, 64 (4) pp. 553-569, which has been published in final form at: http://dx.doi.org/10.1002/glia.22948. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms). |
| Keywords: | T lymphocytes, astrocytes, cytokine, microglia, neuroinflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1502267 |
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