Research at the UKE?
DE
Gagliani Lab
We like studying the basic molecular and cellular mechanisms of T cell biology, adaptation to environmental changes, and ultimately, how T cells either mediate physiological responses to pathogens or pathological tissue damaging processes.
“Unraveling the complexities of CD4+ T cell biology in immune-related disorders.”
Prof. Dr. Nicola Gagliani
Project details and goals
Our laboratory focuses on unraveling the complexities of CD4 T cell biology, in particular their metabolism, adaptability, and roles in disease.
We investigate the different CD4 T cell subsets by exploring their developmental trajectories and the molecular mechanisms underlying their adaptability.
A key aspect of our research is understanding how CD4 T cells adapt to environmental changes, including both classical immune challenges like infections and non-classical stimuli such as dietary shifts. We are particularly interested in the organ-specific responses of resident CD4 T cells and their implications for immune adaptation. Finally, we study the involvement of CD4 T cells in immune-mediated inflammatory diseases and cancer, profiling their interactions with other immune cells, for example macrophages, and with the different tissues at a single-cell level.
Through these efforts, we aim to contribute to a deeper understanding of CD4 T cell function and their potential in treating immune-related disorders.
Current projects – Gagliani Lab
Basic Aspects of CD4+ T Cell Biology
CD4+ T cells are a plastic and heterogeneous population made up of subsets that differ in cytokine production, cell surface markers, function and tissue specificity. Although there have been efforts to classify these subsets based on surface markers and signature cytokines, unsupervised analysis of CD4+ T cell populations shows an unexpected heterogeneity which is not reflected by the classical textbook nomenclature. Supporting this, the use of cytokine fate-mapping mouse models revealed that some CD4+ T cell subsets can adapt their functionality during the development of the immune response. Redefining the classification of CD4+ T cells by understanding their plastic developmental trajectories and identifying the epigenetic and molecular mechanisms controlling these trajectories are some of the main topics of our group.
Immune adaptation of CD4+ T cells to environmental changes
CD4+ T cells possess the ability to switch from a pro- to an anti-inflammatory function, i.e. immune adaptation. The consequences of dysfunctional immune adaptation are clear: the immune cells either fail to mount a protective response to lethal infections, or they overreact to non-harmful antigens and, in doing so, induce a variety of immune-mediated inflammatory diseases (Xu H. et al Nat Comm 2020).
CD4+ T cells adapt in response to both “classical” immune stimuli, such as infections, and “non-classical” immune stimuli, such as changes in dietary habits. In addition, the immune adaptation of CD4+ T cells varies across different organs. There is indeed a conspicuous number of resident CD4+ T cells that have established an intimate and diverse relationship with each organ, which is not yet fully understood.
Our lab is particularly interested in decoding the organ-specific response of resident CD4+ T cells to different classical and non-classical stimuli, with a particular focus on the diet.
The role of CD4+ T cells in immune-mediated inflammatory diseases and cancer
CD4+ T cells are key players in orchestrating a context-appropriate immune response, but their protection comes at a price. They can, in fact, also promote immune-mediated inflammatory diseases (IMIDs), including the development of inflammation-induced carcinogenesis. By profiling resident T cells and their interactions with other immune and non-immune cells in a broad spectrum of diseased human organs at single-cell resolution, we are delineating a new anthology of T cell function in IMIDs and cancer. Using in vitro 3D culture, we validate the newly discovered functions of these cells and provide the scientific and clinical community with new targets for potential future immune therapies.
Team - Gagliani Lab
Prof. Dr. med. ABC ABC
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Key Publications – Gagliani Lab
Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong MN, Kylies D, Gräfe SK, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm AB, Richardt U, Eggert P, Tappe D, Weidemann SA, Ghosh S, Krebs CF, A-Gonzalez N, Worthmann A, Lohse AW, Huber S, Rothlin CV, Puelles VG, Jacobs T, Gagliani N, Bosurgi L
Science. 2024 Apr 5;384(6691):eabo7027.
Short-term dietary changes can result in mucosal and systemic immune depression
Siracusa F#*, Schaltenberg N#, Kumar Y, Lesker TR, Steglich B, Liwinski T, Cortesi F, Frommann L, Diercks BP, Bönisch F, Fischer AW, Scognamiglio P, Pauly MJ, Casar C, Cohen Y, Pelczar P, Agalioti T, Delfs F, Worthmann A, Wahib R, Jagemann B, Mittrücker HW, Kretz O, Guse AH, Izbicki JR, Lassen KG, Strowig T, Schweizer M, Villablanca EJ, Elinav E, Huber S, Heeren J, Gagliani N*
# Co First authors
*Corresponding authors
Nat Immunol. 2023 Aug 14.
Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer
Tintelnot J*, Xu Y, Lesker TR, Schönlein M, Konczalla L, Giannou AD, Pelczar P, Kylies D, Puelles VG, Bielecka AA, Peschka M, Cortesi F, Riecken K, Jung M, Amend L, Bröring TS, Trajkovic-Arsic M, Siveke JT, Renné T, Zhang D, Boeck S, Strowig T, Uzunoglu FG, Güngör C, Stein A, Izbicki JR, Bokemeyer C, Sinn M, Kimmelman AC, Huber S#, Gagliani N*#
*Corresponding authors
# These authors cosuprevised equally to this work
Nature. 2023 Feb 22.
Efferocytosis fuels malignant pleural effusion through TIMP1
Lilan Zhao*, Anastasios D Giannou*, Yang Xu*, Ahmad Mustafa Shiri, Imke Liebold, Babett Steglich, Tanja Bedke, Tao Zhang, Jöran Lücke, Pasquale Scognamiglio, Jan Kempski, Anna Woestemeier, Jing Chen, Theodora Agalioti, Dimitra E Zazara, Diana Lindner, Melanie Janning, Jan K Hennigs, Rajesh M Jagirdar, Ourania S Kotsiou, Sotirios G Zarogiannis, Yasushi Kobayashi, Jacob R Izbicki, Sourav Ghosh, Carla V Rothlin, Lidia Bosurgi#, Samuel Huber#, Nicola Gagliani#
*These authors contributed equally to this work
# These authors cosuprevised equally to this work
Science Adv. 2021 Aug 13;7(33):eabd6734
Single-cell atlas of hepatic T cells reveals expansion of liver-resident naïve-like CD4+ T cells in primary sclerosing cholangitis
Tobias Poch*, Jenny Krause*, Christian Casar, Timur Liwinski, Laura Glau, Max Kaufmann, Annika E Ahrenstorf, Leonard U Hess, Annerose E Ziegler, Glòria Martrus, Sebastian Lunemann, Marcial Sebode, Jun Li, Dorothee Schwinge, Christian F Krebs, Andre Franke, Manuel A Friese, Karl J Oldhafer, Lutz Fischer, Marcus Altfeld, Ansgar W Lohse, Samuel Huber, Eva Tolosa#, Nicola Gagliani#^, Christoph Schramm#^
*These authors contributed equally to this work
#These authors shared senior authorship and ^these are the corresponding authors
J. Hepatol. 2021 Mar 24:S0168-8278(21)00219-1 [https://pubmed.ncbi.nlm.nih.gov/33774059/]
Alumni and former members
- Elham Ahmadyar
- Laura Fromann
- Thao-My Griem
- Bettina Jagemann
- Leonie Konczalla
- Jenny Krause
- Yogesh Kumar
- Friederike Lay
- Dominic Reher
- Nicola Scheibel
- Chiara Sorini
- Gerrit Wolters-Eisfeld
- Lilan Zhao