The Immune Privileged Retina Mediates an Alternative Activation of J774A.1 Cells

Overview

Journal Ocul Immunol Inflamm

Publisher Informa Healthcare

Specialty Ophthalmology

Date 2009 Dec 17

PMID 20001256

Citations 20

Authors

Chun H Lau

Andrew W Taylor

Affiliations

Soon will be listed here.

Abstract

Purpose: We have previously found that retinal pigment epithelial (RPE) cells suppressed endotoxin-stimulated macrophages; moreover, it induced expression of anti-inflammatory cytokines. We further assessed the possibility that the RPE is alternatively activating macrophages.

Methods: J774A.1 cells were stimulated with endotoxin and treated with the conditioned media (CM) of RPE, or neuroretinal eyecups from healthy mouse eyes. The supernatant was assayed for IL-1 beta, TNF-alpha, IL-6, IL-12(p70), and IL-10, and for nitric-oxide generation. The RPE conditioned media (RPE CM) was absorbed of known soluble factors to identify the factor that augments nitric-oxide generation.

Results: We found the RPE CM suppressed all cytokine production except IL-10, and augmented nitric-oxide generation. The augmented nitric-oxide levels were mediated by RPE derived alpha-melanocyte stimulating hormone (alpha-MSH).

Conclusions: Healthy RPE not only suppresses inflammatory activity, it promotes an alternative activation of macrophages that can further promote immune privilege.

Citing Articles

Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.

Wang X, Wang T, Lam E, Alvarez D, Sun Y Int J Mol Sci. 2023; 24(15).

PMID: 37569464 PMC: 10418793. DOI: 10.3390/ijms241512090.

The retina-specific basigin isoform does not induce IL-6 expression in mouse monocytes.

Solstad A, Brown J, Ochrietor J Mol Vis. 2023; 29:13-24.

PMID: 37287642 PMC: 10243675.

Stimulating the Melanocortin System in Uveitis and Diabetes Preserves the Structure and Anti-Inflammatory Activity of the Retina.

Ng T, Taylor A Int J Mol Sci. 2023; 24(8).

PMID: 37108092 PMC: 10138492. DOI: 10.3390/ijms24086928.

Immune Cells in Subretinal Wound Healing and Fibrosis.

Szczepan M, Llorian-Salvador M, Chen M, Xu H Front Cell Neurosci. 2022; 16:916719.

PMID: 35755781 PMC: 9226489. DOI: 10.3389/fncel.2022.916719.

Melanocortin receptor agonists suppress experimental autoimmune uveitis.

Ng T, Dawit K, Taylor A Exp Eye Res. 2022; 218:108986.

PMID: 35196505 PMC: 9050930. DOI: 10.1016/j.exer.2022.108986.

References

Kezic J, Xu H, Chinnery H, Murphy C, McMenamin P . Retinal microglia and uveal tract dendritic cells and macrophages are not CX3CR1 dependent in their recruitment and distribution in the young mouse eye. Invest Ophthalmol Vis Sci. 2008; 49(4):1599-608. DOI: 10.1167/iovs.07-0953. View

Wayne Streilein J, Ma N, Wenkel H, Ng T, Zamiri P . Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Res. 2002; 42(4):487-95. DOI: 10.1016/s0042-6989(01)00185-7. View

Zamiri P, Masli S, Kitaichi N, Taylor A, Wayne Streilein J . Thrombospondin plays a vital role in the immune privilege of the eye. Invest Ophthalmol Vis Sci. 2005; 46(3):908-19. DOI: 10.1167/iovs.04-0362. View

Broderick C, Duncan L, Taylor N, Dick A . IFN-gamma and LPS-mediated IL-10-dependent suppression of retinal microglial activation. Invest Ophthalmol Vis Sci. 2000; 41(9):2613-22. View

Gordon S . Alternative activation of macrophages. Nat Rev Immunol. 2003; 3(1):23-35. DOI: 10.1038/nri978. View

Wayne Streilein J . Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol. 2003; 74(2):179-85. DOI: 10.1189/jlb.1102574. View

Xu H, Chen M, Mayer E, Forrester J, Dick A . Turnover of resident retinal microglia in the normal adult mouse. Glia. 2007; 55(11):1189-98. DOI: 10.1002/glia.20535. View

Strauss O, Stumpff F, Mergler S, Wienrich M, Wiederholt M . The Royal College of Surgeons rat: an animal model for inherited retinal degeneration with a still unknown genetic defect. Acta Anat (Basel). 1998; 162(2-3):101-11. DOI: 10.1159/000046474. View

Delano M, Scumpia P, Weinstein J, Coco D, Nagaraj S, Kelly-Scumpia K . MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007; 204(6):1463-74. PMC: 2118626. DOI: 10.1084/jem.20062602. View

10.

Bunt S, Yang L, Sinha P, Clements V, Leips J, Ostrand-Rosenberg S . Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res. 2007; 67(20):10019-26. PMC: 4402704. DOI: 10.1158/0008-5472.CAN-07-2354. View

11.

Tanihara H, Yoshida M, Matsumoto M, Yoshimura N . Identification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1993; 34(2):413-9. View

12.

Bronte V, Zanovello P . Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005; 5(8):641-54. DOI: 10.1038/nri1668. View

13.

Youn J, Nagaraj S, Collazo M, Gabrilovich D . Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 2008; 181(8):5791-802. PMC: 2575748. DOI: 10.4049/jimmunol.181.8.5791. View

14.

Nagaraj S, Gabrilovich D . Myeloid-derived suppressor cells. Adv Exp Med Biol. 2007; 601:213-23. DOI: 10.1007/978-0-387-72005-0_22. View

15.

Gal A, Li Y, Thompson D, Weir J, Orth U, Jacobson S . Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet. 2000; 26(3):270-1. DOI: 10.1038/81555. View

16.

Gabrilovich D, Nagaraj S . Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009; 9(3):162-74. PMC: 2828349. DOI: 10.1038/nri2506. View

17.

Gregerson D, Heuss N, Lew K, McPherson S, Ferrington D . Interaction of retinal pigmented epithelial cells and CD4 T cells leads to T-cell anergy. Invest Ophthalmol Vis Sci. 2007; 48(10):4654-63. DOI: 10.1167/iovs.07-0286. View

18.

Kezic J, McMenamin P . Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments. J Leukoc Biol. 2008; 84(3):721-9. DOI: 10.1189/jlb.0308166. View

19.

Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M . The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004; 25(12):677-86. DOI: 10.1016/j.it.2004.09.015. View

20.

Finnemann S . Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J. 2003; 22(16):4143-54. PMC: 175805. DOI: 10.1093/emboj/cdg416. View