Local immune cells are on standby in the body’s organs as rapid reaction troops against infections, tumors and inflammations. On site, they specialize and take on different tasks.
When pathogens invade the human body, a rapid response is required. Special immune cells are at the forefront of the immune response. They reside in various tissues such as the lungs, liver, skin and intestines, where they take up the fight against invaders at an early stage. Their name: innate lymphoid cells, or ILCs for short.
A special property of these cells: Unlike many other immune cells, they do not first have to be alerted in order to then migrate to their place of action in the body. Instead, they settle in the tissues and organs shortly after birth and persist there permanently.
mRNA atlas of ILC1 established at the single cell level.
ILCs can arise in tissues from immature progenitor cells and mature into operational immune cells. This was recently shown by scientists of the Max Planck Research Group at the Institute of Systems Immunology of the Julius Maximilians University of Würzburg (JMU). Until now, it was unclear how this maturation takes place in detail. “We wanted to understand how immature ILCs become effector cells that can, for example, kill tumor cells or fight infections with the help of cytokines,” explains Professor Georg Gasteiger, chair and head of the Max Planck Research Group at the Institute of Systems Immunology at JMU. To this end, the Würzburg research team studied the group of ILC1s that play a role in viral infections and in tumor defense. The team mapped all mRNA molecules of individual ILC1 in the liver and created a virtual cell atlas from these analyses.
Task division: supply, helper and killer cells
Based on these “molecular fingerprints,” the researchers recognized that there are specialized cells within ILC1 that share their tasks: “We found cells that can proliferate very rapidly and thus ensure a supply of ILCs. In the process, they specialize into so-called helper or killer ILCs.” Gasteiger’s team found that the helper cells produce a wide range of messenger substances that play a role in the early phase of infections, for example. The killer cells, on the other hand, are armed with molecules that allow them to recognize and kill tumor cells. “Until now, it was thought that these cells were different types of ILCs” explains Christin Friedrich. The postdoctoral researcher from Gasteiger’s team is the first author of the publication, which appeared in the renowned journal Nature Immunology. “But our data show that these are different levels of specialization that can arise in each institution from the same supply forces.”
Can killer ILCs be made therapeutically useful?
“Interestingly, however, ILCs only develop into killer cells in some tissues, although our data show that they have the potential to do so in all tissues” explains Gasteiger. “We have preliminary evidence that this development is actively suppressed in some tissues, possibly to prevent tissue damage or inflammation. We now want to understand how we can therapeutically activate the killer cells, for example, to improve immune control of nascent tumors and metastases. We also want to investigate which molecules the ILCs can use to recognize tumors and how they behave in different tissues during infections.”
Transcription factor Hobit drives specialization
Christin Friedrich adds: “Our work shows how the transcription factor Hobit drives specialization into mature effector cells. Excitingly, Hobit is also expressed in other killer cells of the human immune system. Based on our results, we can now explore the function of Hobit in these defense cells, how they mature, and how they may be driven to target tumors in different tissues.”
Source:
Effector differentiation downstream of lineage commitment in ILC1 is driven by Hobit across tissues. Christin Friedrich, Renske L. R. E. Taggenbrock, Rémi Doucet-Ladevèze, Gosia Golda, Rebekka Moenius, Panagiota Arampatzi, Natasja A. M. Kragten, Katharina Kreymborg, Mercedes Gomez de Agüero, Wolfgang Kastenmueller, Antoine-Emmanuel Saliba, Dominic Grün, Klaas P. J. M. van Gisbergen, Georg Gasteiger. Nature Immunology, August 30, 2021, DOI: 10.1038/s41590-021-01013-0.
