June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
CDCP1 on retinal pigmented epithelial cells facilitates T cell migration into the retina to induce experimental autoimmune uveitis
Author Affiliations & Notes
  • Lingjun Zhang
    Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Ohio, United States
  • Brent A. Bell
    Cole Eye Institute, Cleveland Clinic, Ohio, United States
  • Rachel Caspi
    Laboratory of Immunology, National Eye Institute, National Institute of Health, Maryland, United States
  • Feng Lin
    Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Ohio, United States
    Cole Eye Institute, Cleveland Clinic, Ohio, United States
  • Footnotes
    Commercial Relationships   Lingjun Zhang, None; Brent Bell, None; Rachel Caspi, None; Feng Lin, None
  • Footnotes
    Support  NIH Grant EY025373
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3665. doi:
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    • Get Citation

      Lingjun Zhang, Brent A. Bell, Rachel Caspi, Feng Lin; CDCP1 on retinal pigmented epithelial cells facilitates T cell migration into the retina to induce experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3665.

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

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Abstract

Purpose : To investigate the potential role of CUB domain-containing protein 1 (CDCP1) in the pathogenesis of experimental autoimmune uveitis (EAU).

Methods : Multiple human primary RPE and RPE cell lines were examined for the presence of CDCP1 on the cell surface by flow cytometric analyses. CDCP1 knockdown (KD) RPEs were generated by transfecting the cells with lentivirus encoding CDCP1-specific shRNAs followed by flow sorting. Cytokine production profiles of the WT and CDCP1 KD RPEs were analyzed by ELISA. Both WT and CDCP1 KD RPE monolayers were also used in a transwell-based T cell migration assay. For in vivo experiments, the same numbers of WT uveitogenic T cells were adoptively transferred into naïve WT and CDCP1 KO mice, and the development of EAU was evaluated by various established ocular imaging techniques.

Results : We found that CDCP1 is present on all RPE cells examined and its expression is upregulated after IFNg stimulation. The CDCP1-specific shRNA knocked down the expression of CDCP1 on the transfected RPEs, which resulted in reduced IL-6 production from the cells. In the in vitro T cell migration assays, fewer T cells migrated through the RPE monolayers when their CDCP1 expression was knocked down. More importantly, CDCP1 KO mice developed significantly less severe EAU with markedly reduced numbers of infiltrating leukocytes in the retina as assessed by fundoscopy, optical coherence tomography and ocular histopathological analyses.

Conclusions : CDCP1 is present on RPEs and that it is required for efficient uveitogenic T cell infiltration through the outer blood-retinal barrier for the development of experimental autoimmune uveitis. These new insights suggest that CDCP1 could be a novel target for blocking autoreactive T cell infiltration into the retina for managing autoimmune uveitis.

This is a 2020 ARVO Annual Meeting abstract.

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