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Researchers at the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered that immune cells gradually prepare themselves for quick response to infection during development.

Our immune system comprises of two arms that include innate and adaptive. ILCs are innate immune cells capable of responding immediately against pathogens at the first site of invasion. They emit cytokines, which are small molecules that help transmit signals to combat infection.

NIAMS scientific director John J O’Shea said: "Up until now, researchers have focused on T cells, another type of immune cell.

"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."

The adaptive immune response works more slowly to develop an army of cells that can prevent specific offending pathogens.

Helper T cells in particular are a major part of the adaptive immune system and used to generate different cytokines based on the type of pathogen they are trying to deal with.

Each cell type is unique because of its particular pattern of DNA structure and regulatory factors that can help determine if a gene is active or inactive.

Inactive regions of DNA are twisted into tight coils, while active DNA regions are open and accessible to the cellular machinery that reads the genetic information.

The open regions of the genome include genes themselves, along with several regions that contribute to the regulation of their activities.

The areas of the genome, as well as factors that determine whether or not the information is read, known as the cell’s regulome.

While experimenting on mice, researchers studied the genome regions that control cytokine genes produced by both ILCs and T cells.

The study revealed that each subclass of ILCs is related to a specific pattern of accessible regions. These patterns can be considered as a type of barcode for each subclass.

ILCs acquire their barcodes in a stepwise procedure over the course of cellular development. According to analysis, barcodes are in-place in ILCs before they combat the infection.

This open, accessible configuration surrounding the activities that control cytokine genes can be able to allow ILCs to immediately begin a fight against the infection.

The researchers discovered that several of the DNA regions controlling cytokine genes in the T cells of the mice are inaccessible and silenced before their exposure to a pathogen.

"ILCs and T cells appear very different, but in the end, the way they control key responses is amazingly similar."

In case of infection, T cells adopted barcodes similar to those of their ILC counterparts, which complemented earlier discoveries that stated ILC and T cell subclasses produce similar sets of cytokines.

It also revealed differences in the way the two cell types control the activities of these primary immune response genes.

While ILCs are capable for a quick defence against infection, T cells are minimally prepared when the pathogen invades.

NIAMS post-doctoral fellow Han-Yu Shih said: "ILCs and T cells appear very different, but in the end, the way they control key responses is amazingly similar.

"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."

NIAMS is part of the National Institutes of Health.


Image: Innate lymphoid cells that response rapidly to infection. Photo: courtesy of NIAMS.