Human T-cell immunology—from the mechanistic basis to translational applications
We are a research group interested in the fundamental mechanisms that shape human T cell memory responses in health and disease. Our long-term goal is to develop novel therapeutic strategies in settings of autoimmunity, cancer and chronic infections.
The primary focus of our laboratory is to investigate the regulation of human T cells in health and disease. We address fundamental questions about the mechanistic basis of human T cell memory formation, stabilisation, and modulation. We also investigate T cell communication with the local tissue microenvironment in settings of health and disease. Our research has unravelled novel T cell specialisations, including GM-CSF and IL-1alpha production (Noster et al., Sci Transl Med 2014; Chao et al., Nat Immunol 2023), and anti-inflammatory Th17 cells (Zielinski et al., Nature 2012), with significant implications for chronic infections and the pathogenesis of autoimmune diseases such as multiple sclerosis.
We are particularly interested in the mechanisms by which tissue-resident immunological memory is generated and maintained in human tissue (ERC Grant). The reciprocal interactions of T cells with the tissue microenvironment, including the microbiota, metabolites, and even ions, are of particular interest (Soll et al., Nat Immunol 2024). They shape the functionality of the tissue-resident memory T cell compartment, “imprint” tissue-tropic migration and residence, and represent interesting targets for novel immunomodulatory therapies in settings of autoimmunity, cancer, and chronic infections (de Almeida et al., Sci Immunology 2022).
To address our goals, we use a translational approach, combining the analysis of healthy and pathological tissue samples with novel cutting-edge technologies, gene editing and high-dimensional data analysis. We are studying patients undergoing extensive in vivo perturbation of their immune system, i.e. by systemic therapies with immunomodulatory drugs (biologics) or by stem cell transplantation. We also take advantage of studying patients with genetic immunodeficiency syndromes.
Together, our research aims to provide a fundamental basis for human T cell regulation and to support translational applications for the design of therapeutic targets and adoptive T cell therapies in settings of autoimmunity, infections, and cancer.
Recent Publications
2025
LUBAC modulates CBM complex functions downstream of TRAF6 in T cells. Graß C, Ober F, Sixt C, Moud BN, Antoshkina I, Eberstadt F, Puhach A, Avar G, Keßler A, O’Neill TJ, Seeholzer T, Kranich J, Brocker T, Lammens K, Menden MP, Zielinski CE, Krappmann D. Nat Commun. 2025 Nov 10;16(1):9899. doi: 10.1038/s41467-025-65879-6.PMID: 41213928
Sex differences in sepsis outcomes across the lifespan: a population-based cohort study in Germany. Rose N, Agrama I, Nachtigall I, Pletz MW, Rosendahl J, Chung HY, Zielinski CE, Dudziak D, Spoden M, Dröge P, Hagel S, Fleischmann-Struzek C. Crit Care. 2025 Sep 26;29(1):408. doi: 10.1186/s13054-025-05657-4.PMID: 41013702
Ingestion of mast cell granules boosts macrophages and drives atypical programming. Konstantinos Katsoulis-Dimitriou, Julia Schmidt, Marc Roder, Jan Dudeck, Lars Philipsen, James P Koch, Maria Cattelan, Lea Schmitter, Olga Biskou, Aaron Hoffmann, Michael Mihlan, Rohit Sharma 1, Johanna Kotrba 1, Martin Voss, Mahsa Abedi, Ina Sauerland, Stefan Frischbutter, Christina E Zielinski, Robert Geffers, Tim Lämmermann, Andreas J Müller, Sascha Kahlfuß, Anne Dudeck .J Allergy Clin Immunol 2025 May 26:S0091-6749(25)00576-7.doi: 10.1016/j.jaci.2025.04.035.
2024
Sodium chloride in the tumour microenvironment enhances T-cell metabolic fitness and cytotoxicity. Dominik Soll, Chang-Feng Chu, Shan Sun, Veronika Lutz, Mahima Arunkumar, Mariam Gachechiladze, Sascha Schäuble, Maha Alissa-Alkhalaf, Trang Nguyen, Michelle-Amirah Khalil, Ignacio Garcia-Ribelles, Michael Mueller, Katrin Buder, Bernhard Michalke, Gianni Panagiotou4,11, Kai Ziegler-Martin, Pascal Benz, Philipp Schatzlmaier, Karsten Hiller, Hannes Stockinger, Maik Luu, Kilian Schober, Carolin Moosmann, Wolfgang W. Schamel, Magdalena Huber, Christina E. Zielinski. Nat Immunol (2024). https://doi.org/10.1038/s41590-024-01918-6
The impact of high salt diet on asthma in humans and mice: effect on specific T-cell signatures and microbiome. Stephanie Musiol, Carla P. Harris, Silvia Gschwendtner, Amy Burrell, Yacine Amar, Benjamin Schnautz, Dennis Renisch, Sonja C. Braun, Stefan Haak, Michael Schloter, Carsten B. Schmidt-Weber, Christina E. Zielinski, Francesca Alessandrini. Allergy 2024. DOI: 10.1111/all.16148
Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients. Lilly May, Chang-Feng Chu, Christina E. Zielinski. Cells 2024, 13(4), 300; https://doi.org/10.3390/cells13040300 – 06 Feb 2024
2023
Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Chao YY, Puhach A, Frieser D, Arunkumar M, Lehner L, Seeholzer T, Garcia-Lopez A, van der Wal M, Fibi-Smetana S, Dietschmann A, Sommermann T, Ćiković T, Taher L, Gresnigt MS, Vastert SJ, van Wijk F, Panagiotou G, Krappmann D, Groß O, Zielinski CE. Nat Immunol. 2023 Feb;24(2):295-308. doi: 10.1038/s41590-022-01386-w. Epub 2023 Jan 5. PMID: 36604548; PMCID: PMC9892007.
2022
Human skin-resident host T cells can persist long term after allogeneic stem cell transplantation and maintain recirculation potential. de Almeida GP, Lichtner P, Eckstein G, Brinkschmidt T, Chu CF, Sun S, Reinhard J, Mädler SC, Kloeppel M, Verbeek M, Zielinski CE. Sci Immunol. 2022 Jan 28;7(67):eabe2634. doi: 10.1126/sciimmunol.abe2634. Epub 2022 Jan 28. PMID: 35089814.
Group Leader
Professor of Infection and Immunity at the University of Cambridge
Professor of Infection Immunology at the Leibniz Institut for Natural Product Research and Infection Biology & Friedrich-Schiller-University Jena
Currently recruiting group members.