New Type of Immune Cell Identified in Lung

The ILC2₁₀ cell, so named because it generates the immunoregulatory cytokine IL-10, can be produced following inflammatory signals. It constitutes a previously unknown subset of type 2 innate lymphoid (ILC2) cells, said Jonathan Kaye, PhD, director of the Division of Immunology Research at Cedars-Sinai and senior author of a recent study about the finding, published in Nature Communications.

ILC2 cells play a significant role in immunity to parasitic infections and can repair the lining of the lungs after influenza infections. But they also can initiate and exacerbate inflammatory diseases. Although ILC2₁₀ cells also can be induced in the lung, they do not behave like other cells in this class.

"ILC2₁₀ cells are molecularly distinct from other activated ILC2 cells," Kaye said. "They can suppress recruitment to the lungs of eosinophils—a rare type of immune cell that is implicated in a range of diseases. How they do this is unknown, but it may be by a novel mechanism."

Another unusual feature of the ILC2₁₀ cell population is that it contracts after the stimulus is removed and leaves behind a small group of cells that can be recalled when faced with a later challenge. "In this regard, ILC2₁₀ cells behave more like another type of immune cell—T-cells, which leave behind 'memory cells' after an infection," Kaye said. These memory cells can be rallied to fight a future re-infection.

In the bigger picture, the findings of the study, which were based on mouse-model systems, challenge the traditional distinction between the body's innate immune system and its adaptive immune system. The first system is inborn and acts as the first line of defense against invading foreign substances. The second system molds responses to the specific allergen or pathogen and "remembers" it later. Innate lymphoid cells are part of the innate immune system, and T-cells are part of the adaptive immune system.

"We've thought of the innate immune system as less responsive to the environment than the adaptive immune system, but the new innate cells that we identified seem to be T-cell-like in many respects," said Kaye, who also is vice chair of the Department of Biomedical Sciences and professor of Biomedical Sciences and Medicine.

In ongoing research studies, the investigators are working to identify human ILC2₁₀ cells, which potentially could lead to therapies for a wide range of disorders, including asthma and other inflammatory diseases.

Funding: Research reported in this article was supported by the National Institutes of Health under award numbers 5R21AI124209 and 2R01AI054977.

DOI: 10.1038/s41467-017-02023-z

The IACUC number for animal subjects in research referenced in this article is 5891.