Alina Ulezko Antonova

Program: Immunology

Current advisor: Marco Colonna, MD

Undergraduate university: Emory University

Research summary
I am doing my thesis project in the lab of Dr. Marco Colonna. I use both bioinformatic and cell culture-based approaches to understand the origin, diversity and function of human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are a unique DC subset specialized in the secretion of high amounts of type I interferons (IFN-I, i.e. IFNa and IFNb) immediately after viral infections. These cells correspond to the “natural IFN-producing” cells that were originally reported in human peripheral blood stimulated in vitro with viruses. Production of IFN-I by pDC can be both beneficial and deleterious to human pathology. On the one hand, upon viral encounter or stimulation of toll-like receptors TLR7 and TLR9 with molecules mimicking viral ssRNA and dsDNA, respectively, pDC-derived IFN-I inhibits viral replication and activates both innate and adaptive cellular responses by NK cells, T cells and B cells. On the other hand, dysregulated stimulation of pDCs by endogenous DNA or RNA contributes to excessive secretion of IFN-I in various autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease. Therefore, pDC have important roles in both controlling and initiating human diseases. Interestingly, after the first wave of IFN-I by pDC, other cells sustain high systemic levels of IFN-I, suggesting that pDC have other, yet unknown roles in humans. Additionally, it is plausible that pDC state is influenced by tissue imprinting cues in addition to pathogenic challenges, conferring them tissue-specific functions. The main question I posed is: do pDCs have additional important functions in vivo? To answer this question, we performed Chromium 10X single cell RNA sequencing (scRNAseq) of isolated pDC from different human tissues which allowed me to generate preliminary data on this topic. Our analysis revealed that the tissue microenvironment impacts the transcriptional profile of pDCs, which suggests that circulating pDCs acquire unique transcriptomic features upon seeding into the tissue. One remarkable result of this study is the identification of pDC functional features distinct from the well-known capacity to produce IFN-I and pro-inflammatory cytokines. 
Overall, our work provides a full transcriptomic characterization of human pDC in different human tissues and it provides a window into yet unexplored features of these cells.

Graduate publications

 

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