PD-L1(hi) retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells.
We previously reported that after exposure to inflammatory cytokines, such as IL-17 and IFN-γ, RPE cells express increased amounts of suppressor of cytokine signaling, leading to general suppression of the inflammatory response. Here, we demonstrate that RPE cells expressed increased levels of PD-L1 in response to IL-17, IFN-γ, or Poly I:C. These PD-L1(hi) RPE cells inhibited the pathogenic activities of IRBP-specific T cells, which usually induced uveitis when injected into naïve mice (EAU). The suppressed pathogenicity of these uveitogenic T cells after exposure to PD-L1(hi) RPE cells could be partially reversed by anti-PD-L1 antibodies. Nevertheless, IRBP-specific T cells pre-exposed to PD-L1(hi) RPE cells displayed substantial suppressor activity, which strongly inhibited the activation of fresh IRBP-Teffs in response to subsequent antigenic challenge and when transferred into naïve mice, inhibited the induction of EAU by IRBP-Teff transfer. These findings suggest that inflammatory cytokine-triggered up-regulation of PD-L1 on RPE constitutes a critical factor for inducing infiltrated uveitogenic T cells with regulatory activities, which may accelerate the natural resolution of T cell-mediated intraocular inflammation.
Ke
Yan
Y
Department of Ophthalmology and Vision Sciences, University of Louisville, 301 E. Muhammad Ali Blvd., Louisville, KY 40202, USA. h0shao01@louisville.edu
Sun
Deming
D
Jiang
Guomin
G
Kaplan
Henry J
HJ
Shao
Hui
H
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D020381:Interleukin-17 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010455:Peptides / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D000099214:Retinol-Binding Proteins, Interstitial
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D016207:Cytokines; D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D010455:Peptides; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C498919:Cd274 protein, mouse