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Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis
- Source :
- Ocul Immunol Inflamm
- Publication Year :
- 2023
-
Abstract
- (a). PURPOSE. A central neuropeptide mediator of ocular immune privilege is α-MSH, which can be used to therapeutically suppress experimental autoimmune uveitis (EAU). A part of α-MSH-regulation of immune activity is through its melanocortin 5 receptor (MC5r). One of the mechanisms of ocular immune privilege mediated by α-MSH is RPE suppression of phagolysosome activation associated with antigen presenting cell (APC) processing of antigen. Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of macrophage phagolysosome activation following α-MSH-treatment of EAU. (b). METHODS. The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r((−/−)) mice were used to treat macrophages phagocytizing opsonized-pHrodoRed-bacterial bioparticles to assay for phagolysosome activation. In addition, the phagocytic activity of macrophages from MC5r((−/−)) mice was assayed. (c). RESULTS. The RPE from MC5r((−/−)) mice that have recovered from EAU after α-MSH-therapy do suppress phagosome maturation in wildtype macrophages; but do not suppress phagosome maturation in MC5r((−/−)) macrophages. In addition, α-MSH does not suppress phagolysosome activation in MC5r((−/−)) macrophages, and the macrophages are highly enhanced in their phagocytic activity. Along with the enhanced macrophage activity was observed an increase in damage of the EAU MC5r((−/−)) retinas. (d). CONCLUSION. The results demonstrated that treatment of EAU with α-MSH mediated recovery of RPE suppression of phagolysosome activation in macrophages and protected the retina from inflammatory damage. This was dependent on the expression of MC5r. Moreover, through MC5r the neuropeptide α-MSH potentially acts as a homeostatic moderator of phagosome-maturation within macrophages.
- Subjects :
- Phagocytosis
Immune Privilege
Phagolysosome
Retina
Article
Autoimmune Diseases
Uveitis
03 medical and health sciences
Mice
0302 clinical medicine
Immune privilege
medicine
Immunology and Allergy
Animals
Melanocortin 5 receptor
030203 arthritis & rheumatology
integumentary system
business.industry
Antigen processing
Receptors, Melanocortin
Wild type
medicine.disease
eye diseases
Cell biology
Ophthalmology
alpha-MSH
030221 ophthalmology & optometry
sense organs
business
hormones, hormone substitutes, and hormone antagonists
Homeostasis
Subjects
Details
- ISSN :
- 17445078
- Volume :
- 30
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Ocular immunology and inflammation
- Accession number :
- edsair.doi.dedup.....e99dd703d4ff1777f4069fe441ffb193