Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43
Аутори
Milicevic, KatarinaBataveljic, Danijela
Bogdanović Pristov, Jelena
Andjus, Pavle
Nikolic, Ljiljana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation. However, little is known about the direct interaction between these cells when they are in close proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE) model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells (CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7 receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin reduces the P2X7R-dependent cal...cium response of astrocytes upon encountering CNS-IICs. This interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-IICs. By further defining the interactions between the CNS and the immune system, our findings provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs.
Кључне речи:
astrocytes / calcium signaling / central nervous system autoimmune disease / hemichannel / immune cell / integrin / multiple sclerosis / purinergic receptorsИзвор:
Cells, 2023, 12, 13, 1786-Издавач:
- MDPI
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200053 (Универзитет у Београду, Институт за мултидисциплинарна истраживања) (RS-MESTD-inst-2020-200053)
- Horizon WIDERA 2021—ACCESS-03-01 grant, # 101079355 “BioQantSense”
Напомена:
- casopis je u kategoriji M21
Институција/група
Institut za multidisciplinarna istraživanjaTY - JOUR AU - Milicevic, Katarina AU - Bataveljic, Danijela AU - Bogdanović Pristov, Jelena AU - Andjus, Pavle AU - Nikolic, Ljiljana PY - 2023 UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/2007 AB - In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation. However, little is known about the direct interaction between these cells when they are in close proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE) model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells (CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7 receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-IICs. By further defining the interactions between the CNS and the immune system, our findings provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs. PB - MDPI T2 - Cells T1 - Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43 IS - 13 SP - 1786 VL - 12 DO - https://doi.org/10.3390/cells12131786 ER -
@article{ author = "Milicevic, Katarina and Bataveljic, Danijela and Bogdanović Pristov, Jelena and Andjus, Pavle and Nikolic, Ljiljana", year = "2023", abstract = "In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation. However, little is known about the direct interaction between these cells when they are in close proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE) model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells (CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7 receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-IICs. By further defining the interactions between the CNS and the immune system, our findings provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs.", publisher = "MDPI", journal = "Cells", title = "Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43", number = "13", pages = "1786", volume = "12", doi = "https://doi.org/10.3390/cells12131786" }
Milicevic, K., Bataveljic, D., Bogdanović Pristov, J., Andjus, P.,& Nikolic, L.. (2023). Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43. in Cells MDPI., 12(13), 1786. https://doi.org/https://doi.org/10.3390/cells12131786
Milicevic K, Bataveljic D, Bogdanović Pristov J, Andjus P, Nikolic L. Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43. in Cells. 2023;12(13):1786. doi:https://doi.org/10.3390/cells12131786 .
Milicevic, Katarina, Bataveljic, Danijela, Bogdanović Pristov, Jelena, Andjus, Pavle, Nikolic, Ljiljana, "Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43" in Cells, 12, no. 13 (2023):1786, https://doi.org/https://doi.org/10.3390/cells12131786 . .