# Role of CD6 in the pathogenesis of autoimmune uveitis

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $384,362

## Abstract

Abstract
 Autoimmune posterior uveitis, a common cause of blindness, has an unknown etiology
and no cure is available. Retinal antigen-specific T cell responses, especially Th17 cell
responses, play an important role in the pathogenesis. Although CD6 was identified as a marker
of T cells decades ago, its precise role in T cell regulation and the pathogenesis of diseases
remains elusive, partly due to the lack of CD6 gene-engineered animals. In our pilot studies on
experimental autoimmune uveitis (EAU) in CD6 knockout (KO) mice and using anti-CD6
monoclonal antibodies (mAbs) in wild type mice, we found evidence suggesting that CD6 is a
critical T cell regulator in the pathogenesis of autoimmune uveitis and that targeting of CD6
using mAbs could be effective in treating this disease. In addition, we identified a novel CD6
ligand that could be more important for CD6 function than its currently known ligand (CD166)
and showed that deficiency of this new CD6 ligand leads to attenuated EAU. In this project,
using unique reagents developed by ourselves and provided by our collaborators, including CD6
KO mice, KO mice for either of the two CD6 ligands, CD6 humanized mice, EAU autoantigen-
specific TCR transgenic mice, specific T cell-recognizing tetramers, and mouse anti-mouse CD6
function neutralizing mAbs that cross-react with human CD6, we will study mechanisms by
which CD6 regulates the development of EAU by dissecting its role in regulating autoreactive T
cell activation, proliferation, survival, and infiltration. We will also study the extent to which the
CD6-targeted mAbs ameliorate EAU and the underlying mechanisms. These studies will clarify
the controversy about the role of CD6 in regulating T cells generated by previous in vitro
studies, help in understanding the mechanism by which CD6 regulates autoreactive T cell
responses in the pathogenesis of autoimmune uveitis, and lay a solid foundation for the
development of CD6-targeted mAbs as a new therapy for treating this blinding disease.

## Key facts

- **NIH application ID:** 10085646
- **Project number:** 5R01EY025373-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** FENG C LIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,362
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085646

## Citation

> US National Institutes of Health, RePORTER application 10085646, Role of CD6 in the pathogenesis of autoimmune uveitis (5R01EY025373-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085646. Licensed CC0.

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