Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43
2023
Аутори:
Milićević, KatarinaBataveljić, Danijela
Bogdanović Pristov, Jelena
Anđus, Pavle
Nikolić, Ljiljana
Тип документа:
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 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.
Кључне речи:
astrocytes; calcium signaling; central nervous system autoimmune disease; hemichannel; immune cell; integrin; multiple sclerosis; purinergic receptorsИзвор:
Cells, 2023, 12, 13, 1786-Финансирање / пројекти:
- 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 - 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 - 200053 (Универзитет у Београду, Институт за мултидисциплинарна истраживања) (RS-MESTD-inst-2020-200053)
DOI: 10.3390/cells12131786
ISSN: 2073-4409
PubMed: 37443820