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Tissue-resident T cells and their functional plasticity in coronavirus infections
Summary
Respiratory viruses such as SARS-CoV, MERS-CoV, SARS-CoV-2, and influenza have caused major outbreaks and pandemics and are expected to play a role in future epidemics, including those involving yet unknown viruses. A key factor in the severity of these infections is an overreaction of the immune system, known as a cytokine storm, which can lead to acute respiratory distress syndrome (ARDS) and long-term lung damage. This project focuses on understanding how the immune system - especially virus-specific CD4+ T cells - can either protect the lungs or contribute to this harmful overreaction. Researchers aim to identify the molecular and cellular mechanisms that distinguish protective immune responses from those that drive inflammation and tissue damage.
Special attention is given to tissue-resident CD4+ T cells in the lungs, which can respond quickly to infections but may also become harmful if overstimulated. The project investigates how these T cells develop differently during mild infections, vaccination, or severe immune responses such as cytokine storms. By understanding these processes, the researchers hope to uncover new ways to prevent immune-driven lung damage and to design vaccines that not only protect against infection but also reduce the risk of long-term complications. The findings will be relevant not only for current respiratory viruses but also for future emerging pathogens.
Our Work Packages (WP):
WP1: Development and function of virus-specific CD4+ T cells in the lung - we investigate how CD4+ T cells behave in patients with viral infections and whether their function changes in the context of a cytokine storm.
WP2: Role of CD4+ T cells after vaccination or virus-induced lung inflammation - we test how protective or harmful CD4+ T cells are in vivo, depending on whether they develop after vaccination or during severe viral infection.
These two work packages will help us understand how CD4+ T cells contribute to protection or disease, and how to target them for better therapies and vaccines.
Team
Prof. Dr. Nicola Gagliani
Principal Investigator
E-mail address:
Phone: +49 (0) 40 7410 - 50852
Research Group Gagliani
The Research Group T cell biology, immunity & immune mediated inflammatory diseases is based at the University Medical Center Hamburg-Eppendorf (UKE).
Project related publications
Siracusa F, Schaltenberg N, Kumar Y, …, Huber S, Heeren J, Gagliani N. Short-term dietary changes can result in mucosal and systemic immune depression. Nat Immunol. 2023 Sep;24(9):1473-1486. doi: 10.1038/s41590-023-01587-x.
Tintelnot J, Xu Y, Lesker TR, S…, Riecken K, J…, Kimmelman AC, Huber S, Gagliani N. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer. Nature. 2023 Mar;615(7950):168-174. doi: 10.1038/s41586-023-05728-y.
Zhao Y#, Kilian C#, Turner JE#, Bosurgi L#, …, Schulze zur Wiesch J, …, Addo MM, Lohse AW, Binder M, ..., Huber TB, ..., Panzer U#, Gagliani N#, Krebs CF#. Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. Sci Immunol. 2021. doi: 10.1126/sciimmunol.abf6692.
Poch T, Krause J, Casar C, …, Friese MA, …, Lohse AW, …, Tolosa E, Gagliani N, Schramm C. Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4+ T cells in primary sclerosing cholangitis. J Hepatol. 2021 Aug;75(2):414-423. doi: 10.1016/j.jhep.2021.03.016.
Amezcua Vesely MC, Pallis P, Bielecki P, ..., Esplugues E, Gagliani N#, Flavell R#. Effector T(H)17 Cells Give Rise to Long-Lived T(RM) Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell. 2019. doi: 10.1016/j.cell.2019.07.032.
Krebs CF, Paust HJ, Krohn S, …, Gagliani N, …, Huber S, Turner JE, Panzer U. Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney. Immunity. 2016 Nov 15;45(5):1078-1092. doi: 10.1016/j.immuni.2016.10.020.
Gagliani N, Amezcua Vesely MC, Iseppon A, …, Esplugues E, Huber S, Flavell RA. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature. 2015 Jul 9;523(7559):221-5. doi: 10.1038/nature14452.
#equally contributing authors