de Lima IBQ, Cardozo PL, Fahel JS, Lacerda JPS, Miranda AS, Teixeira AL and Ribeiro FM (2023) Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis. Front. Immunol. 14:1283331. doi: 10.3389/fimmu.2023.1283331
de Lima IBQ, Cardozo PL, Fahel JS, Lacerda JPS, Miranda AS, Teixeira AL and Ribeiro FM (2023) Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis. Front. Immunol. 14:1283331. doi: 10.3389/fimmu.2023.1283331
de Lima IBQ, Cardozo PL, Fahel JS, Lacerda JPS, Miranda AS, Teixeira AL and Ribeiro FM (2023) Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis. Front. Immunol. 14:1283331. doi: 10.3389/fimmu.2023.1283331
de Lima IBQ, Cardozo PL, Fahel JS, Lacerda JPS, Miranda AS, Teixeira AL and Ribeiro FM (2023) Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis. Front. Immunol. 14:1283331. doi: 10.3389/fimmu.2023.1283331
Abstract
Astrocytes have been implicated in a wide range of neurodegenerative diseases, with the literature indicating harmful or beneficial roles on a case-by-case basis. On such conditions, these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including metabotropic glutamate receptor (mGluR5). However, mGluR5 activation in astrocytes under neuroinflammatory conditions can be neuroprotective or have the opposite effect. In this work, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP is capable of reducing pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) release in rTNF-α-stimulated astrocytes, but, in contrast, leads to an augmented expression of the pan-reactive marker SERPINA3. Additionally, CTEP enhances synaptoneurosomes phagocytosis by astrocytes in both non-stimulated and TNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation leads to a reduction in the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockage may have beneficial and detrimental effects under inflammatory conditions.
Keywords
mGluR5; astrocyte; hiPSC; phagocytosis; TNF-α
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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