Special cells prepare for rapid response to infection, NIH reports

(Bethesda, MD – Insurance News and Markets) – The National Institutes of Health (NIH) recently announced that the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NAIMS) have learned about immune cells, called innate lymphoid cells (ILCS) that are prepared for rapid response to infection. The information, published online in “Cell” on May 5, notes that the development and function of the cell type has an important role in the immune response.

Research has focused on T cells and the adaptive immune response, but researchers are looking into ILCs, an innate immune cell that is programmed for quick response to invasion of pathogens, according to John J. O’Shea, MD, senior author of the paper. “ILCs are coming into the spotlight because they appear to have a critical role in defending the body’s barrier regions, such as the skin, lungs, and gut, where microbes must first pass to make their way into the body,” he said.

Rapid response cells (ILCs) mirror the T cells in the kinds of cytokines they produce, but if these are related in other ways, researchers aren’t sure.

Researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered that innate lymphoid cells, early responders of the immune system, are primed at the DNA level for rapid action. Han-Yu Shih and John O’Shea, NIAMS, Alan Hoofring, NIH Division of Medical Arts.

To determine what sets ILCs apart from T cells, Dr. O’Shea’s team looked to the foundation of a cell’s identity — its genetic information, which provides detailed instructions for how a cell functions. Part of what makes each cell type unique is its distinctive pattern of DNA structure and regulatory factors. The combination of a stretch of DNA and a set of regulatory factors can be thought of as a switch — it helps determine whether a gene is turned off (inactive) or on (active).

Working in mice, the researchers analyzed regions of the genome that control the cytokine genes produced by both ILCs and T cells. They found that each subclass of ILCs is associated with a distinct pattern of accessible regions. These patterns can be viewed as a type of barcode for each subclass. Further experiments showed that ILCs acquire their barcodes in a stepwise manner over the course of cellular development.

The so-called barcodes are already in ILCs, even before infections occur. This open, accessible configuration surrounding the switches that control cytokine genes may be instrumental in enabling ILCs to rapidly launch an assault upon infection.

In contrast, the researchers found that many of the DNA regions controlling cytokine genes in the mice’s T cells are inaccessible and silenced prior to exposure to a pathogen. But upon infection, T cells adopted barcodes similar to those of their ILC counterparts.

“ILCs and T cells appear very different, but in the end, the way they control key responses is amazingly similar,” said Han-Yu Shih, Ph.D., a post-doctoral fellow at NIAMS and first author of the paper. “ILCs were discovered less than a decade ago, but the parallels between them and T cells will enable us to more quickly understand how they work and to develop ways to enhance or inhibit their function in treating a variety of immune and inflammatory diseases.”

This work was supported by the NIAMS intramural research program under project number ZIA-AR041159. The National Institute of Allergy and Infectious Diseases and the Beltsville Human Nutrition Research Center also provided support for the study.

Source: National Institutes of Health.