Certain immune cells have different jobs depending on the organ
Group 3 innate lymphoid cells are immune cells that function differently depending on the organ: in the intestines, they prevent certain immune responses, whereas in the spleen they stimulate them. Researchers from the University of Basel have discovered how signals from the surrounding tissue control this. Their findings also play a role in the context of chronic inflammatory bowel diseases.
15 April 2020
Group 3 innate lymphoid cells (ILC3) are part of the innate immune system and can control immune responses through T cells. However, they do this in opposite ways depending on the organ: in the intestine, ILC3s are more likely to block T-cell immune responses, whereas in the spleen they stimulate them. The biological mechanism behind this behavior had not been understood until now. For the first time, in experiments on mice, a research team led by Professor Daniela Finke at theDepartment of Biomedicine, University of Basel, and the University Children's Hospital of Basel has identified tissue-specific signal chains that regulate the contrasting functions of ILC3s.
In the scientific journal Nature Communications, the researchers reported that the microorganisms of the intestinal flora stimulate the local production of a messenger protein, the cytokine interleukin-23 (IL-23). This reduces the ability of ILC3 to interact with T cells and to trigger an immune response. In contrast, tissue in the lymphatic organs, such as the spleen, produces a different messenger protein known as interferon gamma (IFNg), which boosts ILC3’s ability to induce a T-cell immune response.
Signals from the tissue environment
The researchers believe that these messenger substances are responsible for regulating the function of ILC3 cells depending on the situation, which in turn can then control the T-cell immune response in a tissue-specific way. For example, the release of IFNg in the case of an acute infection may improve the properties of ILC3 to activate T cells. IL-23, on the other hand, could also have a therapeutic benefit by suppressing undesirable immune responses (e.g. in cases of chronic inflammation).
These regulatory mechanisms are part of a delicate balance that the immune system must maintain: efficiently combatting pathogens and tumor cells on the one hand, and tolerating the body’s cells and symbiotic microorganisms, such as the intestinal flora, on the other.
Original source
Frank Michael Lehmann, Nicole von Burg, Robert Ivanek, Claudia Teufel, Edit Horvath, Annick Peter, Gleb Turchinovich, Daniel Staehli, Tobias Eichlisberger, Mercedes Gomez de Aguero, Mairene Coto Llerena, Michaela Prchal-Murphy, Veronika Sexl, Mohamed Bentires-Alj, Christoph Mueller & Daniela Finke
Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation
Nature Communications (2020), doi: 10.1038/s41467-020-15612-2
Further information
Prof. Dr. Daniela Finke, University of Basel, Department of Biomedicine, and University Children's Hospital of Basel, tel. +41 61 207 16 34, email: daniela.finke@unibas.ch
