Unraveling the functions of the purinergic receptor P2X7 in experimental autoimmune uveitis (EAU)
Purpose
Uveitis are inflammatory eye diseases of various origins which can be debilitating and lead to blindness. During disease, damaged cells release high levels of extracellular ATP, which constitutes a potent danger signal. The purinergic receptor P2X7 is the main sensor of high amounts of extracellular ATP and its activation triggers an inflammatory response and/or induces cell death. P2X7 expression is increased in various neurodegenerative and autoimmune diseases, in particular P2X7 was shown to be up-regulated in monocytes from patients with Behçet’s disease. Thus, P2X7 may contribute to the development of uveitis via its expression on immune cells. Our data showed that P2X7 is expressed in the different immune cell subpopulations in the retina during EAU. Given the multiple functions of P2X7, its activation could play distinct roles in the development of the disease depending on the cell type that expresses it.
Methods
We investigated the function of P2X7 using active and passive EAU models and new conditional P2X7 knockout mouse strains.
Results
Although we found no significant effect of P2X7 invalidation in T-cells, we showed that the severity of EAU was significantly reduced when P2X7 was specifically depleted in retinal microglia and infiltrating macrophages. The decreased severity was associated with reduced expression of inflammatory mediators.
Conclusion
Thus, targeted inhibition of P2X7 could be a promising therapeutic approach for the treatment of uveitis.
Conflict of interest
No
Authors 1
Last name
DELARASSE
Initials of first name(s)
C
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
Authors 2
Last name
Dechelle-Marquet
Initials of first name(s)
P-A
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
Authors 3
Last name
Lagouge-Roussey
Initials of first name(s)
P
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
Authors 4
Last name
Augustin
Initials of first name(s)
S
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
Authors 5
Last name
Touhami
Initials of first name(s)
S
Department
Hôpital de la Pitié-Salpêtrière - Sorbonne University
City
Paris
Country
France
Authors 6
Last name
Bodaghi
Initials of first name(s)
B
Department
Hôpital de la Pitié-Salpêtrière - Sorbonne University
City
Paris
Country
France
Authors 7
Last name
Guillonneau
Initials of first name(s)
X
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
Authors 8
Last name
Sennlaub
Initials of first name(s)
F
Department
Institut de la Vision - Sorbonne University
City
Paris
Country
France
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