Institute for Molecular and Clinical Immunology, Medical Faculty,
Otto-von-Guericke-University Magdeburg

 

 

Defining the IL-7 niche for local and systemic ILC homeostasis

It is getting increasingly clear that cytokine production by non-hematopoietic stromal cells regulates immune cell development and function, e.g. in the BM and in lymph nodes (LNs). Interleukin-7 (IL-7) is a classical stromal cell-derived cytokine and is crucial for T and B cell development. Importantly, it is also essential for the development and function of innate lymphoid cells (ILCs). IL-7 is produced e.g. in the fetal and inflamed adult liver, the BM and intestine. However, the relative contribution of different IL-7 producing cell types/organs to the modulation of local and systemic ILC responses is unclear. In order to address this question, we will make use of tissue specific IL-7 knockout mice, to inactivate il7 gene activity in the liver, BM and intestine and study local and systemic ILC responses in the steady state and under inflammatory conditions. With the help of this approach we aim to define those cell types that define the IL-7 niche in vivo and regulate ILC homeostasis under physiological and pathophysiological conditions.

 

 

Prof. Dr. Thomas Schüler
Project Leader
Dr. Ute Bank
Postdoc
Amelie Witte
PhD student

 

 

 

 

 

Publications

  1. Schüler, T., G. J. Hämmerling, and B. Arnold. 2004. Cutting edge: IL-7-dependent homeostatic proliferation of CD8+ T cells in neonatal mice allows the generation of long-lived natural memory T cells. J Immunol 172: 15-19.
  2. Sercan, O., G. J. Hämmerling, B. Arnold, and T. Schüler. 2006. Innate immune cells contribute to the IFN-gamma-dependent regulation of antigen-specific CD8+ T cell homeostasis. J Immunol 176: 735-739.
  3. Oelert, T., M. Papatriantafyllou, G. Pougialis, G. J. Hämmerling, B. Arnold, and T. Schüler. 2010. Irradiation and IL-15 promote loss of CD8 T-cell tolerance in response to lymphopenia. Blood 115: 2196-2202.
  4. Shalapour, S., K. Deiser, O. Sercan, J. Tuckermann, K. Minnich, G. Willimsky, T. Blankenstein, G. J. Hämmerling, B. Arnold, and T. Schüler. 2010. Commensal microflora and interferon-gamma promote steady-state interleukin-7 production in vivo. Eur J Immunol 40: 2391-2400.
  5. Sercan, O., D. Stoycheva, G. J. Hämmerling, B. Arnold, and T. Schüler. 2010. IFN-gamma receptor signaling regulates memory CD8+ T cell differentiation. J Immunol 184: 2855-2862.
  6. Shalapour, S., K. Deiser, A. A. Kühl, R. Glauben, S. M. Krug, A. Fischer, O. Sercan, S. Chappaz, S. Bereswill, M. M. Heimesaat, C. Loddenkemper, M. Fromm, D. Finke, G. J. Hämmerling, B. Arnold, B. Siegmund, and T. Schüler. 2012. Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis. PLoS One 7: e31939.
  7. Patra, A. K., A. Avots, R. P. Zahedi, T. Schüler, A. Sickmann, U. Bommhardt, and E. Serfling. 2013. An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development. Nat Immunol 14: 127-135.
  8. Stoycheva, D., K. Deiser, L. Stärck, G. Nishanth, D. Schlüter, W. Uckert, and T. Schüler. 2015. IFN-γ Regulates CD8+ Memory T Cell Differentiation and Survival in Response to Weak, but Not Strong, TCR Signals. J Immunol 194: 553-559.
  9. Bank, U., K. Deiser, D. Finke, G. J. Hämmerling, B. Arnold, and T. Schüler. 2016. Cutting Edge: Innate Lymphoid Cells Suppress Homeostatic T Cell Expansion in Neonatal Mice. J Immunol 
  10. Deiser, K., D. Stoycheva, U. Bank, T. Blankenstein, and T. Schüler. 2016. Interleukin-7 Modulates Anti-Tumor CD8+ T Cell Responses via Its Action on Host Cells. PLOS ONE 11: e0159690.