title: Retinal pericytes inhibit activated T cell proliferation.
abstract: OBJECTIVE
  To test the hypothesis that retinal pericytes (RPCs) are immunosuppressive; therefore, their loss of function under hyperglycemic conditions favors retinal inflammation and contributes to the pathogenesis of diabetic retinopathy (DR).
  
  
  METHODS
  Isolated mouse and human RPCs were tested in T cell function assays to evaluate their capability of inhibiting T cell responses. To elucidate the underlying mechanisms, transwell systems, blocking mAbs against PD-L1 and IL-10 were used. The efficacy of RPCs in protecting retinal endothelial cells (RECs) from inflammation-induced apoptosis was assessed by apoptosis detection staining. Finally, to test whether hyperglycemic conditions impair the immunomodulatory activity of RPCs, RPCs pre-incubated in high glucose or methylglyoxal (MGO) were evaluated using the T cell proliferation assays.
  
  
  RESULTS
  RPCs profoundly inhibited activated T cell proliferation and inflammatory cytokine production. The T cell inhibitory activity of RPCs was decreased, but was not abolished, in transwell experiments. RPCs express PD-L1, and blocking PD-L1 reduced RPCs' efficacy of T cell inhibition. RPCs also produce IL-10, and neutralization of IL-10 reduced their immunosuppressive activity. There were significantly reduced numbers of inflammation-induced apoptosis-detected RECs in the presence of RPCs. Incubation of RPCs with either high glucose or MGO reduced the activity of RPCs to inhibit activated T cell proliferation.
  
  
  CONCLUSIONS
  RPCs are highly immunosuppressive and they protected RECs from inflammation-mediated apoptosis. Hyperglycemic conditions impaired the T cell inhibitory activity of RPCs. These results reveal a new function of RPCs, and its regulation under hyperglycemic conditions. This may represent a novel mechanism by which RPCs contribute to preservation of retinal integrity in diseases, including DR.
authors: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Zhidan
authors: Z
authors: Tu
authors: Yan
authors: Y
authors: Li
authors: Dawn S
authors: DS
authors: Smith
authors: Nader
authors: N
authors: Sheibani
authors: Suber
authors: S
authors: Huang
authors: Timothy
authors: T
authors: Kern
authors: Feng
authors: F
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D003930:Diabetic Retinopathy / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020286:Pericytes / Q000166:cytology* / Q000276:immunology; D012160:Retina / Q000166:cytology* / Q000276:immunology; D012173:Retinitis / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D008565:Membrane Proteins