A large part of our research effort has been to characterize the immunosuppressive and immunoregulating factors within immune privilege tissues. Through immunochemical and biological analysis of aqueous humor, the fluid filling the anterior chamber of the eye, we have identified several potent immunoregulating and immunosuppressing neuropeptides that 1) suppress the activation of effector Th1 cells, 2) suppress the activation and the inflammatory activity of macrophages, and 3) mediate the induction of antigen-specific regulatory T cells.
Our research has found constitutively present neuropeptides in the immune privileged eye, alpha-melanocyte stimulating hormone (a-MSH), vasoactive intestinal peptide, calcitonin gene related peptide, and somatostatin. Collectively, the neuropeptides in aqueous humor suppress activation of delayed type hypersensitivity of adaptive immunity, and endotoxin activation of macrophages in innate immunity. Individually, the neuropeptides target different cells and stages in the induction of an immune response. Also we have preliminary data suggesting a role for the ocular neuropeptides in the regulation of macrophage functionality in the immune privileged eye.
We are finding that within the ocular microenvironment the activation of macrophages to pathogens does not promote inflammation, but promotes suppressor functionality in the macrophages. These macrophages respond to pathogens without mediating inflammation, or activating T cells. Moreover, the macrophages produce anti-inflammatory cytokines, suppress and possibly induce apoptosis in activated T cells, and produce enzymes associated with wound repair. We have preliminary evidence that this is mediated by neurotransmitters of the sympathetic nervous system, norepinephrine and neuropeptide Y along with a-MSH and somatostatin.
As we continue to examine the mechanisms of ocular immune privilege we further promote the importance of the interactions between the nervous and the immune systems and how we can use these interactions to beneficially manipulate immunity.
- Professor, Ophthalmology, Boston University School of Medicine
- Ohio State University, PhD
- Ohio State University, MS
- University of Wisconsin Madison, BS
- Published on 2/1/2017
Wang E, Choe Y, Ng TF, Taylor AW. Retinal Pigment Epithelial Cells Suppress Phagolysosome Activation in Macrophages. Invest Ophthalmol Vis Sci. 2017 Feb 01; 58(2):1266-1273. PMID: 28241314.
- Published on 11/25/2016
Lee DJ, Preble J, Lee S, Foster CS, Taylor AW. MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies Distinct T cell Polarization Programs and a Biphasic Regulatory Response. Sci Rep. 2016 Nov 25; 6:37790. PMID: 27886238.
- Published on 2/8/2016
Taylor AW. Ocular Immune Privilege and Transplantation. Front Immunol. 2016; 7:37. PMID: 26904026.
- Published on 1/25/2016
Clemson CM, Yost J, Taylor AW. The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids. Ocul Immunol Inflamm. 2017 Apr; 25(2):179-189. PMID: 26807874.
- Published on 4/15/2015
Lee DJ, Taylor AW. Recovery from experimental autoimmune uveitis promotes induction of antiuveitic inducible Tregs. J Leukoc Biol. 2015 Jun; 97(6):1101-9. PMID: 25877928.
- Published on 1/29/2015
Taylor AW, Dixit S, Yu J. Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation. Int J Ophthalmol Eye Sci. 2015 Jan 29; Suppl 2(1):1-6. PMID: 25905107.
- Published on 10/29/2014
Bennett JL, Nickerson M, Costello F, Sergott RC, Calkwood JC, Galetta SL, Balcer LJ, Markowitz CE, Vartanian T, Morrow M, Moster ML, Taylor AW, Pace TW, Frohman T, Frohman EM. Re-evaluating the treatment of acute optic neuritis. J Neurol Neurosurg Psychiatry. 2015 Jul; 86(7):799-808. PMID: 25355373.
- Published on 6/21/2014
Ma J, Mehta M, Lam G, Cyr D, Ng TF, Hirose T, Tawansy KA, Taylor AW, Lashkari K. Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation. Mol Vis. 2014; 20:881-93. PMID: 24966660.
- Published on 4/1/2014
Hsu SM, Mathew R, Taylor AW, Stein-Streilein J. Ex-vivo tolerogenic F4/80? antigen-presenting cells (APC) induce efferent CD8? regulatory T cell-dependent suppression of experimental autoimmune uveitis. Clin Exp Immunol. 2014 Apr; 176(1):37-48. PMID: 24266626.
- Published on 9/16/2013
Lee DJ, Taylor AW. Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice. J Immunol. 2013 Oct 15; 191(8):4103-11. PMID: 24043903.
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