Type II‐activated macrophages suppress the development of experimental autoimmune encephalomyelitis

Tierney, Joanna; Kharkrang, Marie; Flamme, Anne Camille La

doi:10.1038/icb.2008.99

Cited by 66 publications

(171 citation statements)

References 27 publications

Supporting

Mentioning

149

Contrasting

Order By: Relevance

“…Analysis of the spinal cord of treated mice showed that SHED-CM induced a shift in the macrophage phenotype from an M1 proinflammatory phenotype to an M2 anti-inflammatory phenotype, as well as suppressed the expression of proinflammatory mediators. Treatments resulting in shifts from M1 to M2 phenotypes were shown to suppress EAE (37,38). In addition, our in vitro analysis indicated that the presence of SHED-CM inhibited the proliferation of…”

Section: Discussionmentioning

confidence: 80%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein–specific CD4+ T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid–binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid–binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.

show abstract

Section: Discussionmentioning

confidence: 80%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Cell-based therapies constitute a promising approach in which cells are differentiated into an immunosuppressive or regulatory phenotype and administered into patients. Experimentally, macrophages have been evaluated as good candidates for cell-based therapeutic intervention not only for atopic and autoimmune diseases, but also for the treatment of kidney diseases (18)(19)(20)(21)(22)(23)(24). Furthermore, regulatory macrophages have been successfully applied to human transplantation patients in first clinical trials to interfere with overt immune responses (25,26) and are discussed as a future therapy in solid-organ transplantation and beyond (27).…”

Section: Discussionmentioning

confidence: 99%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4+ T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4+ T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact–independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.

show abstract

“…Activated macrophages can be broadly classified into classically activated M1 macrophages and alternatively activated macrophages (AAMs or M2). While M1 macrophages are associated with pathologic CNS inflammation in EAE and MS development, M2 macrophages are protective against EAE [13]. IL-33 has recently been shown to promote Th2-cell expansion and skew M1 to the M2 phenotype [14].…”

Section: Introductionmentioning

confidence: 99%

IL‐33 attenuates EAE by suppressing IL‐17 and IFN‐γ production and inducing alternatively activated macrophages

et al. 2012

View full text Add to dashboard Cite

Interleukin (IL)- [26] and is a proinflammatory cytokine in CIA [14,27]. Recent studies have also shown that the IL-33/ST2 pathway plays a significant role in the amplification of M2 polarization and chemokine production, which contribute to innate and antigen-induced airway inflammation [28] and protect against obesity-related metabolic events [29].Interestingly, the highest levels of IL-33 expression in naïve mice are found in the brain and spinal cord [15], indicating that IL-33 may have CNS-specific functions in addition to its role in immune modulation. Astrocytes express both and the expression of IL-33 in the CNS was increased in response to inflammatory stimuli [31]. Recently, it was also reported that IL-33 levels were elevated in the periphery and CNS of MS patients, implicating IL-33 in the pathogenesis of MS [32]. However, the precise role of IL-33 and its receptor in CNS under healthy and inflammatory conditions remain unclear.In the present study, we show that ST2 1C). Quantitative PCR analysis confirmed the upregulation of ST2 expression in Fig. 1B as it clearly shows the enhanced expression of ST2 mRNA in the CNS of mice with EAE compared with that of the naïve mice (Fig. 1D). ST2 −/− mice developed exacerbated EAETo identify an endogenous role of IL-33 in EAE, we next investigated the development of EAE in ST2 −/− mice. EAE was induced in C57BL/6 WT and ST2 −/− mice, Fig. 2A shows that the ST2 −/− mice developed more severe EAE than that in the WT mice. In agreement with many previous reports, BALB/c mice are resistant to the induction of EAE. However ST2 −/− BALB/c mice developed a mild but clearly detectable EAE while the WT BALB/c controls did not (Fig. 2B), the observation was further confirmed by histological analysis of the CNS tissues at day 19 after immunization ( Fig. 2C). Minimal leukocyte infiltration was found in the CNS of WT BALB/c mice whereas significant leukocyte infiltration was found in the submeningeal infiltration in the CNS tissues of ST2 −/− BALB/c mice ( Fig. 2C). IL-33 treatment attenuates EAE developmentWe next investigated the effect of exogenous IL-33 in the development of EAE. C57BL/6 mice were immunized as described in was injected intraperitoneally to each mouse daily from day 12 to day 20 after immunization. Both groups of mice developed similar degree of EAE from day 10 to day 15. However, from day 15, mice treated with IL-33 recovered significantly faster than the control mice treated with PBS ( Fig. 3A). In induced experimental autoimmune diseases, disease severity could vary between experiments even with the same protocol. Analysis using multiple comparisons suggests that the effect of IL-33 treatment on the outcome of EAE mice could be time revealed marked reduction of infiltrating cells in the spinal cord tissues of IL-33-treated mice (Fig. 3B). Importantly, IL-33 had no effect on the disease development in ST2 −/− C57BL/6 mice ( Fig. 3C) demonstrating the specificity of the IL-33 effect. IL-33 alters the cytokine production of EAE miceTo investigate the i...

show abstract

Type II‐activated macrophages suppress the development of experimental autoimmune encephalomyelitis

Cited by 66 publications

References 27 publications

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

IL‐33 attenuates EAE by suppressing IL‐17 and IFN‐γ production and inducing alternatively activated macrophages

Contact Info

Product

Resources

About