Boning Cai
Pronouns: he/his/him
Research Mentor(s): Wentao Wang
Research Mentor School/College/Department: Department Civil and Environmental and Engineering / Engineering
Program: UROP
Session: Session 7 (4:40pm – 5:30pm)
Authors: Jocelyn Cai, Kenneth Gu, Jie Luo
Abstract
Retinoic acid (RA) signals via retinoic acid receptors (RARs), which bind to retinoic acid response elements (RAREs) found in regulatory regions of many genes. The retinoic acid receptor alpha (RARa) is highly expressed in immune cells and previous studies have shown that liganded RARa promotes a tolerogenic CD4 T cell phenotype. However, the role of the RA-RARa axis in CD8 T cells is less well understood. Tumor cells can produce high levels of RA, which may affect T cell-dependent anti-tumor immunity. Our lab recently observed that mice with a T cell specific RARa depletion show improved anti-tumor immunity, while an overexpression of RARa in T cells makes mice more susceptible to cancer growth. We further found that in addition to regulating genes under the control of RAREs, RARa impacts the function of the activator protein-1 (AP-1) family, which is an important family of transcription factors controlling T cell function. To understand the mechanism of how RA and RARa affects CD8 T cells differentiation and function, naïve CD8 T cells from the spleen of WT, RARa-deficient and RARa-overexpressed mice were isolated and cultured under various conditions. The addition of RA to CD8 T cells reduced the viability and differentiation in a RARa-dependent manner. Furthermore, we observed that the addition of RA regulates transcription factors, necessary for T cell differentiation and memory formation, including AP-1 family members. While RA especially influenced initial CD8 T cell differentiation, RA still has an impact on the transcription profile when added at later stages. Our findings deepen our understanding of the function of the RA-RARa axis in CD8 T cells and may improve anti-tumor therapies.
