June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Expression of The Regulatory Melanocortin-Adenosinergic Pathway in Human Uveitis Patients
Author Affiliations & Notes
  • Darren J Lee
    Ophthalmology, Boston University School of Med, Boston, MA
  • Footnotes
    Commercial Relationships Darren Lee, None
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Investigative Ophthalmology & Visual Science June 2015, Vol.56, 888. doi:
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      Darren J Lee; Expression of The Regulatory Melanocortin-Adenosinergic Pathway in Human Uveitis Patients. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):888.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Mice that have recovered from experimental autoimmune uveoretinitis (EAU) have regulatory immunity in their spleen. This post-EAU regulatory immunity involves an APC that activates antigen-specific inducible Treg cells. It requires expression of melanocortin 5 receptor (MC5r) on the APC, and adenosine 2A receptor (A2Ar) on the T cells. This melanocortin-adenosinergic pathway induced regulation provides long-term protection from recurrence of EAU. Therefore, this conserved pathway is a potential therapeutic approach for uveitis. PBMC were assayed to determine whether MC5r and A2Ar are expressed on immune cells in uveitis patients.

Methods: PBMC were collected from healthy volunteers and uveitis patients being treated at Massachusetts Eye Research and Surgery Institute. Patients were grouped as suppressed (US) and active (UA), based on the location of uveitis, and by the type of immunosuppressive therapy. US patients had no uveitis within a year from the time of collection. PBMC were analyzed by FACS for CD14, CD16, CD4, MC5r, and A2Ar expression. The CD4 T cells were sorted out, and the monocytes were sorted into classical (CD14+CD16lo) and non-classical (CD14-CD16hi) subsets. The monocytes were pulsed with tetanus toxin and treated with the neuropeptide α-MSH to stimulate the melanocortin pathway. The T cells were added to the cultures, and the supernatants were assayed for TGF-β.

Results: Analysis of PBMC from US (n = 11) and UA (n = 21) patients and healthy volunteers (n = 9) revealed a similar percentage of classical and non-classical monocytes. Further analysis of MC5r expression on each of the subsets showed no significant difference. The expression of A2Ar on CD4+ T cells was also similar. There was no difference in MC5r or A2Ar expression with age, type of therapy, or location of uveitis. Both monocyte subsets produced slightly more TGF-β from US (n = 5) and UA (n = 6) patients compared to healthy volunteers (n = 3), and treatment with α-MSH had no effect. When T cells were added to the monocyte cultures a similar pattern of TGF-β production was observed.

Conclusions: While our initial functional analysis saw no effect on TGF-β production, the potential to activate the melanocortin-adenosinergic pathway to suppress effector T cells should be possible in uveitic patients.

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