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IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo
- Source :
- Journal of Neuroinflammation
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Background Myeloid cells, such as macrophages and microglia, play a crucial role in neuroinflammation and have been recently identified as a novel therapeutic target, especially for chronic forms. The general aim would be to change the phenotype of myeloid cells from pro- to anti-inflammatory, favoring their tissue-trophic and regenerative functions. Myeloid cells, however, display a number of functional phenotypes, not immediately identifiable as pro- or anti-inflammatory, and associated to ambiguous markers. Methods We employed in vitro assays to study macrophage polarization/differentiation in the presence of classical polarizing stimuli such as IFNγ (pro-inflammatory) and IL4 (anti-inflammatory). We induced neuroinflammation in mice by immunization with a myelin antigen and treated diseased mice with intracisternal delivery of an IL4-expressing lentiviral vector. We analyzed clinical, pathological, and immunological outcomes with a focus on myeloid cells. Results We found that IL6, usually considered a pro-inflammatory cytokine, was released in vitro by macrophages treated with the anti-inflammatory cytokine IL4. We show the existence of macrophages expressing IL6 along with classical anti-inflammatory markers such as CD206 and demonstrate that these cells are immunosuppressive in vitro. In neuroinflamed mice, we show that IL4 delivery in the central nervous system (CNS) is associated with clinical and pathological protection from disease, associated with increased IL6 expression in infiltrating macrophages. Conclusions IL6 is known to mediate both pro- and anti-inflammatory effects, having two distinct ways to induce cell-signaling: either through the membrane bound receptor (anti-inflammatory) or through trans-signaling (pro-inflammatory). We show here that IL6-expressing macrophages are associated to protection from neuroinflammation, suggesting that IL6 anti-inflammatory properties prevail in the CNS, and calling for a general reconsideration of IL6 in macrophage polarization. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0596-5) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Macrophage
Immunology
Autoimmunity
Inflammation
Biology
M2 macrophage
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
In vivo
medicine
Animals
M2 macrophages
skin and connective tissue diseases
Coculture Technique
Interleukin 6
Inflammation Mediator
Cells, Cultured
Interleukin 4
Neuroinflammation
Neuroscience (all)
Dose-Response Relationship, Drug
Microglia
EAE
Animal
Interleukin-6
Macrophages
Research
General Neuroscience
IL4
Phenotype
Coculture Techniques
IL6
In vitro
Cell biology
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Neurology
biology.protein
Female
Interleukin-4
Inflammation Mediators
medicine.symptom
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 17422094
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroinflammation
- Accession number :
- edsair.doi.dedup.....2ec096612fc59b01c5c7814d6197855b