About

Daria Esterhazy is an Assistant Professor in the Department of Pathology at the University of Chicago. She is affiliated with multiple committees including Immunology, Cancer Biology, Microbiology, and Molecular Metabolism and Nutrition. Originally from Vienna, Austria, Professor Esterhazy completed her PhD at ETH Zurich, Switzerland in 2010. She then pursued postdoctoral fellowships at ETH Zurich (2011-2012), UT Southwestern (2012-2013), and The Rockefeller University (2013-2018). Her academic background also includes an MSci and a B.A. from the University of Cambridge, UK. The information provided does not include specific details about her research focus or key contributions.

Research topics

• Medicine
• Immunology
• Biology
• Pathology
• Anatomy
• Internal medicine
• Endocrinology
• Neuroscience

Selected publications

• Tissue-specific tolerance mechanisms and lymph node co-drainage shape T cell immunity in the upper digestive system and pancreatic cancer progression

  Cell Reports · 2026-05-01

  articleOpen accessSenior author

  The liver, pancreas, and duodenum share lymph nodes (LNs), providing a unique system to examine how tissue origin of self-antigens shapes T cell fate. Comparing mice expressing ovalbumin (OVA) from distinct subcellular compartments, we found that cytosolic OVA from the liver or pancreas, but not gut, was immunologically ignored. High-dose hepatic-secreted OVA triggered antigen-specific T cell deletion, whereas secreted pancreatic and intestinal OVA induced regulatory T (Treg) cells, revealing immunological ignorance, clonal deletion, and Treg cell generation as tissue-specific tolerance mechanisms. Of these, LN co-drainage only influenced Treg cell induction, establishing gut-pancreas-liver axes: intestinal viral infection rendered hepatocyte- and exocrine pancreas-specific T cells inflammatory and liver injury promoted pancreas- and gut-directed responses. These self-reactive T cells caused tissue destruction but enhanced pancreatic tumor control when neoantigen OVA was secreted, but not cytosolic. Thus, LN co-drainage and tissue-specific tolerance mechanisms jointly shape immune homeostasis and disease susceptibility in the upper digestive system.

  PublisherDOI

• Medullary stromal cells define small intestinal lymph node identity in humans and mice

  Cell Reports · 2025-10-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  Lymph nodes (LNs) along the murine gastrointestinal tract are immunologically distinct. Here, we investigate whether such an immune dichotomy globally defines gut LN identity and what drives the regional differences. However, we find that, transcriptionally, it is genes associated with stromal cells that define LN location along the intestine, with high conservation between human and mouse. Using LN single-cell RNA sequencing databases and imaging, we pinpoint the underlying reason for our transcriptional signature: a selective enrichment in the small intestine-draining LN medulla for fibroblastic reticular cell subpopulations implicated in extracellular matrix remodeling and stromal cell replenishment, lymphatic endothelial cells, and macrophages. In mice, the unique medullary cellular network is established around weaning age by vitamin A, while the gut microbiota regulates the effect’s amplitude. Our study implicates the LN medulla as contributing to tissue-specific immunity and uncovers privileged access to lipid-soluble vitamins as the pivotal driving force for small intestinal LN architecture. • Gut lymph nodes differ most in their stromal cell composition • This is true in humans and mice • This difference is induced by vitamin A and amplified by the microbiota Fatkhullina et al. discover that in humans and mice, the dominant difference between lymph nodes draining the small intestine versus colon and other sites is their stromal cell and macrophage composition. This difference is induced by dietary vitamin A and amplified by the microbiota.

  PublisherDOI

• Intestinal lymphatic vasculature is functionally adapted to different drainage regions and is altered by helminth infection

  The Journal of Experimental Medicine · 2025-06-12 · 1 citations

  articleOpen accessSenior author

  We sought to determine whether the lymphatic vasculature functionally adapts to the organ in which it resides, such as along the gut. Duodenal lymphatic capillaries (lacteals) displayed the most discontinuous tight junction composition within the gut, resulting in a dependence on duodenal lacteals for rapid dietary lipid uptake. Duodenal helminths abrogated these features. Parallel RNA sequencing of lymphatic endothelial cells and mucosa along the intestine revealed that the transcriptomes overlapped in functional profiles. RNA sequencing also identified a putative VEGFR-2/3 signaling gradient that may explain differences in lacteal tight junctions along the small intestine at homeostasis. Transcriptionally, helminth infection triggered antimicrobial and angiogenic responses. While microbial depletion acted additively to helminths on lymphatic restructuring, glucocorticoids partially reversed helminth-induced lacteal changes. This suggests helminths induce lymphangiogenesis and associated lymphatic "zippering" via inflammation. Our study uncovers and explains the superior lipid absorption by duodenal lacteals and how it is compromised by helminths and provides transcriptional insights into lymphatic function along the gut.

  PublisherOA PDFDOI

• Tissue-specific tolerance mechanisms and lymph node co-drainage converge to shape T cell immunity in the upper digestive system and regulate pancreatic cancer progression

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-05

  articleOpen accessSenior authorCorresponding

  The liver, pancreas, and duodenum share lymph nodes (LNs), providing a unique system to examine how tissue origin of self-antigens shapes T cell fate. Comparing mice expressing ovalbumin (OVA) from distinct subcellular compartments, we found that cytosolic OVA from liver or pancreas, but not gut, was immunologically ignored. High-dose hepatic secreted OVA triggered antigen-specific T cell deletion, whereas secreted pancreatic and intestinal OVA induced regulatory T (Treg) cells, revealing immunological ignorance, clonal deletion and Treg cell generation as tissue-specific tolerance mechanisms. Of these, LN co-drainage only influenced Treg cell induction, establishing gut-pancreas-liver axes: Intestinal viral infection rendered hepatocyte- and exocrine pancreas-specific T cells inflammatory; liver injury promoted pancreas- and gut-directed responses. These self-reactive T cells caused tissue destruction but enhanced pancreatic tumor control when neoantigen OVA was secreted but not cytosolic. Thus, LN co-drainage and tissue-specific tolerance mechanisms jointly shape immune homeostasis and disease susceptibility in the upper digestive system.

  PublisherOA PDFDOI

• Dendritic Cells in the Gastrointestinal System: Division of Labor, Plasticity, and Niche‐Specific Adaptation

  Immunological Reviews · 2025-12-25 · 2 citations

  articleOpen accessSenior authorCorresponding

  The intestinal immune system is constantly challenged to distinguish between innocuous dietary antigens, commensal microbiota and intestinal self-antigens (self-Ags) versus harmful pathogens and malignant cells. It resides in the intestinal wall itself, Peyer's patches (PPs) and the draining lymph nodes (LNs). Dendritic cells (DCs) are found in all of these structures and are professional antigen-presenting cells (APCs) dictating and maintaining T cell fate. Here, we review how DCs contribute to immune homeostasis in the gastrointestinal system through multiple strategies: division in labor and strategic anatomical positioning between DC subtypes, plasticity and site-specific functional adaptation. While these properties of DCs are likely not unique to the gastrointestinal tract, it is the site where we have learned most about how this DC network operates.

  PublisherOA PDFDOI

• T cell fate is dictated by different antigen presenting cells in response to dietary <i>versus</i> gut epithelial self-antigen

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-07 · 2 citations

  preprintOpen accessSenior authorCorresponding

  We investigated whether T cell responses and antigen-presenting cell (APC) requirements in gut-draining lymph nodes differ by antigen source, diet versus epithelium. Using mice fed ovalbumin (OVA) or expressing secreted (s), cytosolic (c), or transmembrane (tm) epithelial OVA, we compared OVA-specific T cell fates. At baseline and after reovirus infection, T cell responses were comparable across models. However, helminth infection induced Th2 cell polarization in sOVA and tmOVA but not cOVA or OVA-fed mice. BATF3⁺ APCs were indispensable for CD4⁺ T cell proliferation only in cOVA mice yet drove Treg cell differentiation across all epithelial OVA models. In contrast, antigen presentation by RORγt⁺MHC-II⁺ APCs was exclusively required for Treg cell induction by dietary OVA. These distinct APC dependencies correlated with susceptibility to pathology elicited by dietary versus epithelial self-antigens. Thus, antigen origin and presentation context are integrated to shape T cell fate, a new framework for predicting gut immune outcomes.

  PublisherOA PDFDOI

• Immune crosstalk via shared lymph nodes in the upper digestive system influences pancreatic adaptive immunity and alters disease progression 2302

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Lymph nodes (LNs) are strategically positioned to achieve site-specific adaptive immunity. In the upper digestive system, however, LNs are shared by distinct organs – liver, pancreas and duodenum. We previously showed that intestinal infections can alter β-cell-reactive T cell fate via this co-drainage. To explore the immune modulatory role of this shared anatomy beyond β-cell immunity, we created three mouse lines expressing OVA as a self-antigen upon tissue-specific Cre recombination, with distinct subcellular locations (secretory, cytosolic or transmembrane). Using OT-I/II T cell transfers, we found that both tissue properties and antigen location dictated immune visibility. Cytosolic OVA in the liver and pancreas, but not the gut, needed apoptosis-inducing agents to elicit T cell proliferation in LNs, while other OVA forms triggered T cell responses at homeostasis. Intestinal viral infection increased liver- and exocrine-pancreas-specific TH1 cells and cytotoxic lymphocytes, while liver perturbation led to more pancreas- and gut-specific TH1 cells at the expense of Treg in co-drained LNs. Pancreas-reactive cytotoxic T cells infiltrated the tissue, causing autoimmune tissue destruction but improved tumor control. The study offers a tool for investigating self-reactivity in cell types with specific Cre drivers and highlights the extensiveness of the immune crosstalk in the upper digestive system via LN sharing, with implications for pancreatic and hepatic disease modulation. Funding Sources Supported by NIH R01 DK133393 Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases

  Mucosal Immunology · 2025-05-19 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Identification of antigen-presenting cell–T cell interactions driving immune responses to food

  Science · 2024-12-19 · 57 citations

  articleOpen access

  The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4 + T cells and inducing their differentiation into regulatory (peripheral regulatory T cell) or inflammatory [T helper (Th) cell] subsets. We used a proximity labeling method (LIPSTIC) to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions and to understand cellular mechanisms by which tolerance to food is induced and can be disrupted by infection. Helminth infections disrupted tolerance induction proportionally to the reduction in the ratio between tolerogenic APCs—including migratory dendritic cells (cDC1s) and Rorγt + APCs—and inflammatory APCs, which were primarily cDC2s. These inflammatory cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific Th2 responses.

  PublisherDOI

• Inducible, but not constitutive, pancreatic <i>REG/Reg</i> isoforms are regulated by intestinal microbiota and pancreatic diseases

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-22

  preprintOpen accessSenior authorCorresponding

  Abstract The REG / Reg gene locus encodes for a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether REG/Reg family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in human and mouse, pancreas and gut differed in REG / Reg isoform levels and preferences, with duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select Reg members in gut and pancreas. These Reg members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as “inducible” and others as “constitutive”. Indeed, also in models of pancreatic-ductal adenocarcinoma and pancreatitis, only inducible Reg members were upregulated in pancreas. While intestinal Reg expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of REG / Reg isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated Reg response.

  PublisherOA PDFDOI

Recent grants

• Immune crosstalk through shared LN drainage in the digestive system

  NIH · $1.8M · 2022–2027

Frequent coauthors

• Daniel Mucida

  Rockefeller University

  12 shared

• Markus Stoffel

  ETH Zurich

  11 shared

• Emanuele de Rinaldis

  Sanofi (United States)

  7 shared

• Venu Pullabhatla

  Oxford Gene Technology (United Kingdom)

  4 shared

• G.N. Yakovlev

  MRC Mitochondrial Biology Unit

  4 shared

• Martin S. King

  4 shared

• Ruedi Aebersold

  ETH Zurich

  4 shared

• Ainsley Lockhart

  Rockefeller University

  4 shared

Labs

• Esterházy LabPI