Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis

Pardo, Evelyn; Cárcamo, Claudia; Martín, Reinaldo Uribe San; Ciampi, Ethel; Segovia-Miranda, Fabián; Curkovic-Peña, Cristobal; Montecino, Fabián; Holmes, Christopher P.; Tichauer, Juan E.; Acuña, Estefanía Flores; Osorio‐Barrios, Francisco; Castro, M Delgado; Cortés, Pablo; Oyanadel, Claudia; Valenzuela, David M.; Pacheco, Rodrigo; Naves, Rodrigo; Soza, Andrea; González, Alfonso

doi:10.1371/journal.pone.0177472

Cited by 40 publications

(38 citation statements)

References 87 publications

(166 reference statements)

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“…For CCL3 and LGALS8, lower blood levels were related with EDSS progression. In a recent study, LGALS8 was shown to have immunosuppressive protective role in CNS inflammation, by balancing the Th17 and Th1 cells . Moreover, LGALS8 was shown to be present in CSF of MS patients, and RRMS patients with antibodies against LGALS8 showed EDSS progression and worse disease prognosis .…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, LGALS8 was shown to have immunosuppressive protective role in CNS inflammation, by balancing the Th17 and Th1 cells . Moreover, LGALS8 was shown to be present in CSF of MS patients, and RRMS patients with antibodies against LGALS8 showed EDSS progression and worse disease prognosis . Interestingly, potential imbalance in peripheral Th17 and Th1 cells has also been shown to be associated with reduced gene expression of several different cytokines and chemokines in MS patients, among which CCL3 .…”

Section: Discussionmentioning

confidence: 99%

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Plasma proteome in multiple sclerosis disease progression

Malekzadeh¹,

Leurs

Wieringen³

et al. 2019

Ann Clin Transl Neurol

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Background: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression. Methods:We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapseonset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models. Results: Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 9 10 À5 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 9 10 À9 , q = 1,70 9 10 À6 ), FGF9 (P = 3,42 9 10 À9 , q = 1,70 9 10 À6 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways. Conclusions: Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS. 1582

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma proteome in multiple sclerosis disease progression

Malekzadeh¹,

Leurs

Wieringen³

et al. 2019

Ann Clin Transl Neurol

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“…Galectin-8 that also has the tandemrepeat-type architecture exerts similar immunosuppressive responses as galectin-9 does in EAE. Fittingly, EAE is exacerbated in Lgals8 −/− mice, by modulating the balance of Th17 and Th1 cells and their Tregs [288]. This galectin induces apoptosis in Th17, but not Th1 cells, and galectin-8 administration ameliorates EAE [288].…”

Section: Reduced Alternative Macrophages Activationmentioning

confidence: 99%

“…Fittingly, EAE is exacerbated in Lgals8 −/− mice, by modulating the balance of Th17 and Th1 cells and their Tregs [288]. This galectin induces apoptosis in Th17, but not Th1 cells, and galectin-8 administration ameliorates EAE [288]. In the clinical situation, the possibility for the occurrence of auto-antibodies against galectins should be considered (see below, [289,290]).…”

Section: Reduced Alternative Macrophages Activationmentioning

confidence: 99%

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The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis

Jong

Gabius

Baron

2019

Cell. Mol. Life Sci.

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Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. Currently approved disease-modifying treatment modalities are immunomodulatory or immunosuppressive. While the applied drugs reduce the frequency and severity of the attacks, their efficacy to regenerate myelin membranes and to halt disease progression is limited. To achieve such therapeutic aims, understanding biological mechanisms of remyelination and identifying factors that interfere with remyelination in MS can give respective directions. Such a perspective is given by the emerging functional profile of galectins. They form a family of tissue lectins, which are potent effectors in processes as diverse as adhesion, apoptosis, immune mediator release or migration. This review focuses on endogenous and exogenous roles of galectins in glial cells such as oligodendrocytes, astrocytes and microglia in the context of de-and (re)myelination and its dysregulation in MS. Evidence is arising for a cooperation among family members so that timed expression and/or secretion of galectins-1, -3 and -4 result in modifying developmental myelination, (neuro)inflammatory processes, de-and remyelination. Dissecting the mechanisms that underlie the distinct activities of galectins and identifying galectins as target or tool to modulate remyelination have the potential to contribute to the development of novel therapeutic strategies for MS.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Galectin‐8 inhibition and functions in immune response and tumor biology

Purić,

Nilsson,

Anderluh

2024

Medicinal Research Reviews

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Galectins are among organisms' most abundantly expressed lectins (carbohydrate‐binding proteins) that specifically bind β‐galactosides. They act not only outside the cell, where they bind to extracellular matrix glycans, but also inside the cell, where they have a significant impact on signaling pathways. Galectin‐8 is a galectin family protein encoded by the LGALS8 gene. Its role is evident in both T‐ and B‐cell immunity and in the innate immune response, where it acts directly on dendritic cells and induces some pro‐inflammatory cytokines. Galectin‐8 also plays an important role in the defense against bacterial and viral infections. It is known to promote antibacterial autophagy by recognizing and binding glycans present on the vacuolar membrane, thus acting as a danger receptor. The most important role of galectin‐8 is the regulation of cancer growth, metastasis, tumor progression, and tumor cell survival. Importantly, the expression of galectins is typically higher in tumor tissues than in noncancerous tissues. In this review article, we focus on galectin‐8 and its function in immune response, microbial infections, and cancer. Given all of these functions of galectin‐8, we emphasize the importance of developing new and selective galectin‐8 inhibitors and report the current status of their development.

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Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis

Cited by 40 publications

References 87 publications

Plasma proteome in multiple sclerosis disease progression

Plasma proteome in multiple sclerosis disease progression

The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis

Galectin‐8 inhibition and functions in immune response and tumor biology

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