Alina Ulezko Antonova

Program: Immunology

Current advisor: Marco Colonna, MD

Undergraduate university: Emory University, 2019

Enrollment year: 2020

Research summary
Novel features of human plasmacytoid dendritic cells

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
Yomogida K, Trsan T, Sudan R, Rodrigues PF, Ulezko Antonova A, Ingle H, Luccia BD, Collins PL, Cella M, Gilfillan S, Baldridge MT, Oltz EM, Colonna M. 2024 The transcription factor Aiolos restrains the activation of intestinal intraepithelial lymphocytes. Nat Immunol, 25(1):77-87. PMCID:

Cao S, Fachi JL, Ma K, Ulezko Antonova A, Wang Q, Cai Z, Kaufman RJ, Ciorba MA, Deepak P, Colonna M. 2024 The IRE1?/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease. J Clin Invest, 134(13):e174198. PMCID: PMC11214543

Ulezko Antonova A, Fachi JL, Gilfillan S, Colonna M. 2023 The thin line between conventional dendritic cells (cDCs) and group 3 innate lymphoid cells (ILC3s) in the gut. Int Immunol, 35(3):107-121. PMCID: PMC10210749

Panda SK, Peng V, Sudan R, Ulezko Antonova A, Di Luccia B, Ohara TE, Fachi JL, Grajales-Reyes GE, Jaeger N, Trsan T, Gilfillan S, Cella M, Colonna M. 2023 Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes. Immunity, 56(4):797-812.e4. PMCID: PMC10101911

He M, Roussak K, Ma F, Borcherding N, Garin V, White M, Schutt C, Jensen TI, Zhao Y, Iberg CA, Shah K, Bhatia H, Korenfeld D, Dinkel S, Gray J, Ulezko Antonova A, Ferris S, Donermeyer D, Lindestam Arlehamn C, Gubin MM, Luo J, Gorvel L, Pellegrini M, Sette A, Tung T, Bak R, Modlin RL, Fields RC, Schreiber RD, Allen PM, Klechevsky E. 2023 CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses. Science, 379(6633):eabg2752. PMCID: PMC10424698

Hou J, Zhou Y, Cai Z, Terekhova M, Swain A, Andhey PS, Guimaraes RM, Ulezko Antonova A, Qiu T, Sviben S, Strout G, Fitzpatrick JAJ, Chen Y, Gilfillan S, Kim DH, Van Dyken SJ, Artyomov MN, Colonna M. 2023 Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination. Cell Rep, 42(4):112293. PMCID: PMC10511667

Ulezko Antonova A, Lonardi S, Monti M, Missale F, Fan C, Coates ML, Bugatti M, Jaeger N, Fernandes Rodrigues P, Brioschi S, Trsan T, Fachi JL, Nguyen KM, Nunley RM, Moratto D, Zini S, Kong L, Deguine J, Peeples ME, Xavier RJ, Clatworthy MR, Wang T, Cella M, Vermi W, Colonna M. 2023 A distinct human cell type expressing MHCII and ROR?t with dual characteristics of dendritic cells and type 3 innate lymphoid cells. Proc Natl Acad Sci USA, 120(52)::e2318710120. PMCID: PMC10756205