Researchers Uncover Immune Functions of Innate Lymphoid Cells

The human immune system is broken down into two primary pathways – the innate system, which acts as the body’s first line of defense and does not differentiate between different types of pathogens, and the adaptive system, which is a type of immunity that gradually builds up over time with disease exposure or vaccination. Cells part of the innate immune system, including 2 innate lymphoid cells (ILC2s), form a line of defense against pathogens within mucous membranes of the respiratory tract and intestine. The exact functions behind these innate immune cells have remained poorly understood, so researchers from Charité – Universitätsmedizin Berlin helped shed light on these specialized cells.

“Innate lymphoid cells were discovered a decade or so ago and we already know a lot about them, but their exact function in the machinery of the immune system is not yet completely understood,” says senior author Dr. Christoph Klose, who heads the Emmy Noether Independent Junior Research Group on the regulation of type 2 immune responses by neuropeptides and neurotransmitters at the Institute of Microbiology, Infectious Diseases and Immunology at Charité. “There is a group of adaptive immune cells – namely the T cells – that carry out some similar functions as part of the type 2 immune response, so it was previously thought that the role of ILC2s may be redundant and could be easily taken over by the T cells.”

The team’s work, published in the journal Nature, challenges this long-held belief. With single-cell sequencing methods and animal models, the team was able to assess cells’ molecular state individually. With such high resolution, the team was able to observe some of the central functions of ILC2s. “A certain type of immune cells called eosinophils were not able to develop properly when ILC2s were absent,” states Dr. Klose. “This relationship was previously unknown and came as a big surprise.”

Eosinophils were shown to be involved in inflammation and mucus production within epithelial cells. This dramatically impacts the body’s ability to successfully expel parasites from the body. “The absence of ILC2s was clearly noticeable in our tests examining the immune response to worm infections. There was only limited mucus production in the tissue and the parasites could no longer be combated effectively,” explains Dr. Klose.

The team also examined symptoms of allergic asthma in their models and found that, overall, symptoms improved when ILC2s were removed. “This could be a starting point for future studies aimed at developing potential allergy therapies,” says Dr. Klose. “With our study, we were able to show that group 2 innate lymphoid cells are essential cogs in the machinery of the immune system and cannot be replaced without compromising the immune response.”

For future work, Dr. Klose and his team want to investigate whether innate lymphoid cells regulate other aspects of the immune system.