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Systems Immunology Würzburg

Mucosal Immunology (Zimmermann Lab)


The Zimmermann lab is interested in the dynamic regulation of CD4 T cell responses against non-pathogenic commensal bacteria in the gut and other mucosal surfaces. For this, we have developed innovative gnotobiotic approaches such as defined, temporally and spatially controlled colonisation of germ-free mice. We complement these with newly engineered immunological tools such as adoptive transfer of commensal-specific CD4 T cells and peptide : MHC tetramers but also classical assays such as multicolor flow cytometry, immunofluorescence microscopy, and scRNA-seq. Our aim is to understand how such microbiota-induced CD4 T cells contribute to barrier protection but may also fuel inflammatory bowel disease (IBD) when dysregulated. We envision that our work might aid mucosal vaccination approaches and identify novel therapeutic targets in IBD. To improve diagnostics, the group also develops novel sequencing- and cytometry-based methods to interrogate the gut microbiota.

We are a young & enthusiastic team with an interest in innovative technical solutions to questions in the field that values curiosity, diversity, and collaboration.

Microbiota-specific CD4 T cell memory

The human intestine is home to the densest accumulation of microbes on earth – the gut microbiota – and the last 2 decades have revealed that our immune system actively engages with these mostly beneficial inhabitants. CD4 T cells are important immune cells induced by the gut microbiota and crucial for maintaining intestinal homeostasis. While beneficial for barrier protection, dysregulated CD4 T cell responses to the gut microbiota can result in chronic inflammation as in inflammatory bowel disease (IBD). Whereas long-lived memory T cells are critical components of vaccine-induced protection, it has remained elusive whether non-pathogenic gut commensals also induce T cell memory. Understanding this may be key for better mucosal immunisation and understanding disease relapses in quiescent IBD.

In this project funded by an ERC Starting Grant, we combine newly developed models of transient colonisation of germ-free mice by prototypic gut commensals with cutting-edge immunological tools to understand how non-pathogenic gut bacteria induce long-lived tissue-resident CD4 T cell memory. Our main questions are (1) how such Th cells are maintained and regulated in the tissue, (2) how their phenotype is shaped by host and microbial factors during induction and challenge, and (3) what their physiological importance is for epithelial homeostasis, barrier protection, and control of luminal bacteria. Overall, this project shall elucidate the regulation of microbiota-specific memory Th cells to eventually enhance mucosal vaccine design and enable the selective targeting of IBD-perpetuating Th cells.


Publications (selection)

Full publication list J.Zimmermann

F. Schmidt*, J. Zimmermann*, T. Tanna*, R. Farouni, T. Conway, A. J. Macpherson*, R. J. Platt*, Noninvasive assessment of gut function using transcriptional recording sentinel cells. Science 376, eabm6038 (2022). *equal contribution

C. Stehle, T. Rückert, R. Fiancette, D. W. Gajdasik, C. Willis, C. Ulbricht, P. Durek, M.-F. Mashreghi, D. Finke, A. E. Hauser, D. R. Withers, H.-D. Chang, J. Zimmermann*, C. Romagnani*, T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation. Nat Immunol 22, 1231–1244 (2021). *equal contribution

B. Yilmaz*, C. Mooser*, I. Keller*, H. Li, J. Zimmermann, L. Bosshard, T. Fuhrer, M. G. de Agüero, N. F. Trigo, H. Tschanz-Lischer, J. P. Limenitakis, W.-D. Hardt, K. D. McCoy, B. Stecher, L. Excoffier, U. Sauer, S. C. Ganal-Vonarburg, A. J. Macpherson, Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice. Cell Host Microbe 29, 650-663.e9 (2021). *equal contribution

K. Gronke*, P. P. Hernández*, J. Zimmermann, C. S. N. Klose, M. Kofoed-Branzk, F. Guendel, M. Witkowski, C. Tizian, L. Amann, F. Schumacher, H. Glatt, A. Triantafyllopoulou, A. Diefenbach, Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature 566, 249–253 (2019). *equal contribution

J. Zimmermann, P. Durek, A. A. Kühl, F. Schattenberg, P. Maschmeyer, F. Siracusa, K. Lehmann, K. Westendorf, M. Weber, R. Riedel, S. Müller, A. Radbruch, H. Chang, The intestinal microbiota determines the colitis-inducing potential of T-bet-deficient Th cells in mice. Eur. J. Immunol. 48, 161–167 (2017).

J. Zimmermann*, T. Hübschmann*, F. Schattenberg, J. Schumann, P. Durek, R. Riedel, M. Friedrich, R. Glauben, B. Siegmund, A. Radbruch, S. Müller, H. Chang, High-resolution microbiota flow cytometry reveals dynamic colitis-associated changes in fecal bacterial composition. Eur. J. Immunol. 46, 1300–1303 (2016). *equal contribution

J. Zimmermann, A. A. Kühl, M. Weber, J. R. Grün, J. Löffler, C. Haftmann, R. Riedel, P. Maschmeyer, K. Lehmann, K. Westendorf, M.-F. Mashreghi, M. Löhning, M. Mack, A. Radbruch, H. D. Chang, T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis. Mucosal Immunol 9, 1487–1499 (2016).

J. Zimmermann, A. Radbruch, H. Chang, A Ca2+ concentration of 1.5 mM, as present in IMDM but not in RPMI, is critical for maximal response of Th cells to PMA/ionomycin. Eur. J. Immunol. 45, 1270–1273 (2015).

We’re hiring!

Check “Team” for details.

ERC Starting Grant for Research on Immunological Memory in the Gut

2023 ERC Starting Grant 101116766 “GuT Memory – Engineered symbionts elucidate gut T cell memory and its (dys)regulation”

- Open postdoc position in immunology

- Open PhD position in immunology

Interested in doing your Master thesis at the exciting interphase of immunology and the microbiota with us? 

Please reach out! Positions for Master theses are not officially announced but continuously offered depending on the current capacity of the group.

Dr. Jakob Zimmermann

Junior Group Leader