People

Daria Esterhazy, PhD

Immunological niches in the digestive system



We study how immune homeostasis is maintained in the digestive system, and how its failure can lead to diseases such as food allergies, inflammatory bowel diseases (IBD), autoimmune diseases and cancer. In particular the lab explores immunologically distinct niches within the digestive system, studies how they are created by dietary, commensal colonization and infection history in the course of a lifetime, and what the systemic impact of each niche may be. We are analyzing the impact on the innate and adaptive immune system at the physiological, cellular and molecular level.



Gastrointestinal lymphatic system.

One key aspect we are studying is the gastrointestinal lymphatic system and how compartmentalized lymphatic drainage along the gut helps create different immunological environment. For example, we have found previously that gut segment specific infection (helminths in the upper small intestine versus bacteria in the colon) leads to dysfunction of only selective lymph nodes. We are currently expanding our studies to other pathogens and members of the commensal microbiome, but also to different dietary regimes, as nutrients are taken up in a site-selective manner as well. Most notably, the lymphatics of the upper small intestine are responsible for the absorption of dietary lipids and other hydrophobic nutrients and molecules. Both lymph fluid composition but also lymphatic architecture are influenced by these environmental factors, and likely help create distinct milieus. This may help sustain homeostatic conditions, but also support the chronicity of pathological conditions such as the metabolic syndrome, cancers or IBD.



Pancreas and other branches of the digestive system.

The digestive system also includes the pancreas, mesentery, and by extension liver, gall bladder, and the draining lymph nodes, of which several happen to be shared by these organs. We are interested in how the immune system of all these branches is influenced by gut luminal contents, and how it may communicate. This may occur via deliberate or inappropriate leakage of migratory immune cells, macro- and micro-molecules traveling through the interstitial space, common lymphatics or blood vessels. Through our studies we hope to better understand how for example gastrointestinal infections may trigger pathologies such as type 1 diabetes.

Techniques used in the laboratory.

We used a wide range of techniques including microsurgery, lymphatic vessel cannulation, pancreatic islet isolation, live and light sheet imaging of the vascular and immune systems, single cell analysis, mass spectrometry, and genetic manipulation of mice.



In sum, our studies help define how tissue environments are created and influence the local immune system. While we focus on the digestive system, the concept that the concerted action of site specific exogenous factors, inherent tissue properties and connectivity to other organs determines the immunological output is likely relevant for other parts of the body as well. A more differentiated understanding of what shapes an immunological niche may help us devise more refined and effective therapeutic strategies to target organ-specific diseases.

The Rockefeller University
- Postdoctoral Fellowship
2018

Howard Hughes Medical Institute
- Postdoctoral Fellowship
2013

ETH Zurich
Switzerland
- Postdoctoral Fellowship
2012

ETH Zurich
Zurich, Switzerland
PhD - metabolism, pancreatic islet biology
2010

University of Cambridge
Cambridge, UK
MSci - Biochemistry
2006

University of Cambridge
Cambridge, UK
BA - Natural Sciences
2005

Compartmentalized gut lymph node drainage dictates adaptive immune responses.
Esterházy D, Canesso MCC, Mesin L, Muller PA, de Castro TBR, Lockhart A, ElJalby M, Faria AMC, Mucida D. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature. 2019 05; 569(7754):126-130.
PMID: 30988509

Gut immune cells have a role in food metabolism.
Esterházy D, Mucida D. Gut immune cells have a role in food metabolism. Nature. 2019 02; 566(7742):49-50.
PMID: 30710125

SnapShot: Gut Immune Niches.
Mucida D, Esterhazy D. SnapShot: Gut Immune Niches. Cell. 2018 09 06; 174(6):1600-1600.e1.
PMID: 30193116

Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules.
Cohen LJ, Esterhazy D, Kim SH, Lemetre C, Aguilar RR, Gordon EA, Pickard AJ, Cross JR, Emiliano AB, Han SM, Chu J, Vila-Farres X, Kaplitt J, Rogoz A, Calle PY, Hunter C, Bitok JK, Brady SF. Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2018 04 04; 556(7699):135.
PMID: 29620727

Commensal bacteria make GPCR ligands that mimic human signalling molecules.
Cohen LJ, Esterhazy D, Kim SH, Lemetre C, Aguilar RR, Gordon EA, Pickard AJ, Cross JR, Emiliano AB, Han SM, Chu J, Vila-Farres X, Kaplitt J, Rogoz A, Calle PY, Hunter C, Bitok JK, Brady SF. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2017 09 07; 549(7670):48-53.
PMID: 28854168

Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
Esterházy D, Loschko J, London M, Jove V, Oliveira TY, Mucida D. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance. Nat Immunol. 2016 May; 17(5):545-55.
PMID: 27019226

Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.
Loschko J, Schreiber HA, Rieke GJ, Esterházy D, Meredith MM, Pedicord VA, Yao KH, Caballero S, Pamer EG, Mucida D, Nussenzweig MC. Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. J Exp Med. 2016 Apr 04; 213(4):517-34.
PMID: 27001748

Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry.
Katafuchi T, Esterházy D, Lemoff A, Ding X, Sondhi V, Kliewer SA, Mirzaei H, Mangelsdorf DJ. Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry. Cell Metab. 2015 Jun 02; 21(6):898-904.
PMID: 26039452

Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Brown CC, Esterhazy D, Sarde A, London M, Pullabhatla V, Osma-Garcia I, Al-Bader R, Ortiz C, Elgueta R, Arno M, de Rinaldis E, Mucida D, Lord GM, Noelle RJ. Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program. Immunity. 2015 Mar 17; 42(3):499-511.
PMID: 25769610

Phenotype and function of nasal dendritic cells.
Lee H, Ruane D, Law K, Ho Y, Garg A, Rahman A, Esterházy D, Cheong C, Goljo E, Sikora AG, Mucida D, Chen BK, Govindraj S, Breton G, Mehandru S. Phenotype and function of nasal dendritic cells. Mucosal Immunol. 2015 Sep; 8(5):1083-98.
PMID: 25669151

View All Publications

Advanced Postdoctoral Fellowship
Swiss National Science Foundation
2014 - 2016

Helmsley Trust Postdoctoral Fellowship
The Rockefeller University
2013 - 2014

Early Mobility Postdoctoral fellowship
Swiss National Science Foundation
2012 - 2013

Young Scientist Research Prize
Swiss Diabetes Foundation
2012

ETH Medal for PhD Thesis
ETH Zurich
2012

Gonville and Caius College Scholarship
University of Cambridge
2002 - 2006

Cambridge European Trust Scholarship
University of Cambridge
2002 - 2006