Innate lymphoid cells (ILCs) participate in tissue homeostasis, inflammation, and early immunity against infection. However, it is not fully understood how ILCs acquire effector function and whether these mechanisms differ between organs. Now, researchers from the Max Planck Research Group at the Institute of Systems Immunology of Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, report ILCs can arise in tissues from immature precursor cells and mature into operational immune cells.

Their findings are published in the journal Nature Immunology, in a paper titled, “Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues.”

“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,” explained Georg Gasteiger, PhD, chair and head of the Max Planck Research Group at the JMU Institute of Systems Immunology.

The researchers studied the group of ILCs that play a role in viral infections and in tumor defense. “Through multiplexed single-cell mRNA sequencing, we identified cKit+CD127hiTCF-1hi early differentiation stages of T-bet+ ILC1s. These cells were present across different organs and had the potential to mature toward CD127intTCF-1int and CD127TCF-1 ILC1s,” the researchers wrote.

The researchers discovered cells that can multiply very quickly and thus provide for replenishment of ILCs. In the process, they specialize into so-called helper or killer ILCs.

“Until now, it was thought that these cells were different types of ILCs,” explained 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 they are different degrees of specialization that can arise in each organ from the same supply troops.”

“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,” explained Gasteiger.

“We have initial evidence that this development is actively suppressed in some tissues, possibly to avoid tissue damage or inflammation. We now want to understand how we can therapeutically activate the killer cells, for example to improve immune control of developing 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.”

“Our work shows how the transcription factor Hobit drives specialization to mature effector cells,” added Christin Friedrich. “It is exciting that Hobit is also expressed in other killer cells of the human immune system. Based on our results, the function of Hobit in these defense cells can now be explored, how they mature and how they might be induced to fight tumors in different tissues.”

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