Table 3.
Galectins during MS-relevant inflammation
| Galectin | Model | Main result | Mechanism | References |
|---|---|---|---|---|
| In vivo | ||||
| gal-1 | EAE (GP-BP, female Lewis rats, treatment before or at induction) | Inhibits clinical and histological signs, most effective when applied at induction | Prevents sensitization of encephalitogenic GP-BP-specific T cells and induces timely expression of suppressor CD8 + T cells | [268] |
| gal-1 | EAE (MOG35−55, female Lgals1−/− 129/Sv mice) | Exacerbated disease severity | Increases pathogenic Th1 and Th17 responses | [269] |
| EAE (MOG35−55, C57Bl/6 mice, treatment after immunization but before disease onset) | Ameliorates disease severity | Reduces the numbers of IL-17 and IFNγ-producing CD4+ T cells | ||
| gal-1 | EAE (MOG35−55, female Lgals1−/− C57Bl/6 mice) | Not reported | Enhances classical microglia activation, promotes axonal damage | [212] |
| EAE (MOG35−55, female Lgals1−/− C57Bl/6 mice, adoptive transfer WT astrocytes) | Ameliorates disease severity | Regulates microglial activation | ||
| EAE (MOG35−55, female C57Bl/6 mice, treatment around onset clinical disease) | Ameliorates disease severity | Decreases microglial activation, prevents neurodegeneration and demyelination and reduces GFAP expression | ||
| EAE (MOG35−55. female Lgals1−/− C57Bl/6 mice, adoptive transfer of treated control and LPS-stimulated microglia) | Ameliorates disease severity | Prevents microglia activation | ||
| gal-3 | EAE (MOG35−55, Lgals3−/− C57Bl/6 mice) | Slightly delayed onset and ameliorated disease severity | Decreases IL-17 and IFNγ levels, increases the development of Th2 and Treg cells | [272] |
| gal-4 | chronic relapsing EAE (rrMOG1–125, in male Dark Agouti rats) | Increased presence in inflammatory infiltrates | Localizes to ED1 + cells at relapse phase | [179] |
| gal-8 | EAE (MOG35−55, Lgals8−/− C57BL/6NTac mice) | Faster onset and increased disease severity | Increases Th17 polarization and decreases the frequency of Treg cells that impact Th17 | [288] |
| EAE (PLP139–151, female C57BL/6 mice, treatment at induction) | Delayed onset and ameliorated disease severity | Apoptotic elimination of activated Th17 cells | ||
| gal-9 | EAE (MOG35−55, female C57BL/6J mice, treatment after immunization but before disease onset) | Ameliorates disease severity | Eliminates IFNγ producing Th1 cells through Tim3 | [282] |
| EAE (MOG35−55 SJL/J mice, injection at induction) | Exacerbates disease severity | |||
| In vitro | ||||
| gal-1 | Human bone marrow mesenchymal stem cells (MSCs) | MSC-derived gal-1 inhibits T-cell proliferation | Binds to NP-1 on T cells | [213, 271] |
| gal-1 | Primary microglia (C57BL/6 WT and Lgals1−/− C57Bl/6 mice mice, treatment) | Deactivates classically activated microglia | Controls microglial activation through p38MAPK, CREB and NF-κB signaling pathways and promotes microglial deactivation by retaining CD45 at the surface | [212] |
| gal-3 | Blood monocyte-derived human macrophages | Gal-3 expression and proteolytic processing are higher in alternatively activated cells, while its secretion is higher in classically activated macrophages | Not determined | [280] |
| gal-3 | Microglia and astrocytes (primary cells, Sprague–Dawley rats, BV2 microglia cell line, treatment) | Enhances production of pro-inflammatory mediators | Triggers the JAK-STAT signaling cascade through IFNRG1(CRD-independent, IFNγ-independent) | [226] |
| gal-3 | Bone marrow- and blood monocyte-derived macrophages (129Sv WT and Lgals3−/− mice, THP-1 monocytic cell line) | Reduced alternative macrophages activation | Mediates alternative activation by PI3K activation upon binding to CD98 | [279] |
| gal-9 | Primary microglia, astrocyte and mixed glial cultures (Sprague–Dawley rats, C57Bl/6J WT and Lgals9−/− mice) | Astrocyte-derived gal-9 enhances microglia TNF production | Tim-3 independent | [299] |
| poly(I:C-) treated microglia stimulate gal-9 mRNA expression in astrocytes | Mediated via a heat-sensitive microglia secreted factor | |||
EAE experimental autoimmune encephalomyelitis, gal galectin, GFAP glial fibrillary acidic protein, GP-BP guinea pig myelin basic protein, IL interleukin, LPS lipopolysaccharide MOG myelin oligodendrocyte glycoprotein, MSC mesenchymal stem cells, NP-1 neuropilin-1, poly(I:C) polyinosinic:polycytidylic acid, siRNA small interfering RNA, Tim-3, T-cell immunoglobulin and mucin domain-containing molecule-3, Th T helper, TNF tumor necrosis factor, WT wild-type