The role of an orphan scavenger receptor (CD163L1) in T cells 2310079

Abstract

Abstract Introduction It is becoming increasingly clear that the developmental origins of T cells play a major role in their subsequent phenotypes. However, we lack markers to distinguish fetal- and adult-derived T cells. Using multiple RNA-seq datasets, we found CD163L1 to be selectively expressed by fetal-derived CD8+ T cells. CD163L1 is a member of the scavenger receptor cysteine-rich superfamily and has been shown to be expressed by γδ T cells. However, its role in the immune system is not known. Therefore, we developed several novel tools to determine the expression and function of CD163L1 across lymphocyte populations. Methods We hypothesized that CD163L1 would be preferentially expressed by innate-like lymphocytes made in early life. To test this, we generated a monoclonal antibody against CD163L1 and used it to characterize its expression across multiple lymphocyte subsets in tissues from mice of different ages. To understand its function, we generated a CD163L1 knockout mouse model using CRISPR—Cas9 system. Results Our results indicate that CD163L1 is expressed on many subsets of lymphocytes (e.g., NK cells, γδ T cells, αβ T cells) that are produced in early life and migrate to epithelial barriers, particularly the skin. Interestingly, lymphocyte subsets that express CD163L1 exhibit distinct effector molecules (FasL, IL13) and CD8+ T cells lacking CD163L1 are more efficient at forming memory. These data suggest that CD163L1+ lymphocytes may play a role in the removal of damaged cells and immune regulation. Conclusion CD163L1 expression defines a more innate-like and regulatory phenotype across distinct lymphocyte lineages. We are currently performing single-cell sequencing to gain deeper insight into the role of CD163L1+ lymphocytes during viral infection and autoimmune skin conditions. Funding Source R21AI167858 and CVG Scholars award 2023-2024 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)