Regulatory Circuits Mediated by Lectin-Glycan Interactions in Autoimmunity and Cancer

Rabinovich, Gabriel A.; Croci, Diego O.

doi:10.1016/j.immuni.2012.03.004

Cited by 295 publications

(313 citation statements)

References 124 publications

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“…13 Our recent studies revealed that Gal-1 induces microglia deactivation and prevents inflammation-induced neurodegeneration. 20 In the present study, we successfully uncoupled the microglial deactivating effect, which was observed using both WT and monomeric Gal-1 from the neuroregenerative effect, which was verified only when high concentrations of WT Gal-1 were used.…”

Section: Discussionmentioning

confidence: 99%

“…This lectin exists in a monomer-dimer equilibrium depending on its relative concentration and biochemical features of different tissues. 13 Within the CNS, Gal-1 controls proliferation of adult neural progenitor cells, 14,15 regulates neurogenesis and promotes functional recovery after stroke. 16 Expression of Gal-1 correlates with the regenerative potential of spinal motoneurons after SCI.…”

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confidence: 99%

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Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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“…It has been shown that the interaction between endogenous glycan-binding proteins and glycosylated receptors is of crucial importance for immunological homeostasis (reviewed in ref. 69 ). Within these processes, galectins emerge as important regulators in several physiological and pathological processes (reviewed in Blidner and Rabinovich).…”

Section: Modulators Of the Immune Responses During Pregnancymentioning

confidence: 99%

Adaptive Immune Responses During Pregnancy

Zenclussen

2013

American J Rep Immunol

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It has long been believed that there is no immune interaction between mother and conceptus during pregnancy. This concept changed after evidence was provided that the maternal immune system is aware of the semiallogeneic conceptus and develops strategies to tolerate it. Since then, finely regulated mechanisms of active tolerance toward the fetus have been described. This Special Issue of the American Journal of Reproductive Immunology deals with these mechanisms. It begins with the description of minor histocompatibility antigens in the placenta; it further goes through adaptive immune responses toward paternal fetal antigens, mostly concentrating on regulatory T cells and molecules modulating the Th1/Th2 balance. The participation of antibody‐producing B cells in normal and pathological pregnancies is also discussed. This introductory chapter resumes the concepts presented throughout the Issue and discusses the clinical applications raised from these concepts.

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“…The most common and well-defined form of programmed cell death is apoptosis, which is a physiological cell-suicide pro-gramme that is essential for embryonic development (Campos-Ortega and Hartenstein, 2013), immune-system function (Abbas et al, 2012) and the maintenance of tissue homeostasis (Sonnenberg et al, 2011) in multi-cellular organisms. Deregulation of apoptosis has been implicated in numerous pathological conditions, including neurodegenerative diseases (Radi et al, 2014), autoimmunity and cancer (Rabinovich and Croci, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Zhu²,

Sun

et al. 2017

J. Toxicol. Sci.

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-3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway. Our results clearly showed that 3-MCPD treatment inhibits cell proliferation and reactive oxygen species generation. qPCR-array indicated that nine apoptotic genes were up-regulated more than 2-fold and six down-regulated more than 2-fold. Genes associated with the mitochondrial apoptotic pathway, especially BCL2 family genes, changed significantly, indicating that the mitochondrial apoptotic pathway is activated. Death receptor pathway-related genes, TNFRS-F11B and TNFRSF1A, changed significantly, indicating that the death receptor pathway is also activated, resulting in the inhibition of cell growth and proliferation as well as induction of apoptosis. To sum up, the experiment results indicated that 3-MCPD induced HEK293 cell toxicity through the death receptor pathway and mitochondrial pathway.

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Regulatory Circuits Mediated by Lectin-Glycan Interactions in Autoimmunity and Cancer

Cited by 295 publications

References 124 publications

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Adaptive Immune Responses During Pregnancy

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

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