Researchers from Japan’s RIKEN Center for Integrative Medical Sciences (IMS) have shown how the body suppresses the activation of long-lived cells after infection. The findings, published in Nature Immunology, might help find a way to prevent dangerous allergic inflammatory responses caused by unnecessarily prolonged immune responses. The innate immune response, which is the body’s non-specific response to pathogens, was once believed to be a simple system relying on short-lived effector cells alone, but it is now known to be more complex, involving long-lived lymphoid cells.
Such long-lived cells can be problematic, for example in the case of parasitic worms. These worms, known as helminths, are a formidable challenge to human health, being a major cause of mortality in the developing world.
The body’s key defense against these parasites and some fungal infections, called the type 2 innate immune response, actually turns out to be a double-edged sword, as it has been implicated in allergic inflammatory responses such as asthma caused by fungal infections. While this immune response is important, it can be dangerous if it lasts beyond its necessity, said Dr. Kazuyo Moro, team leader of the Laboratory for Innate Immune Systems in IMS.
“It was once believed that the response was mainly mounted by short-lived cells, but now we know that it also involves a population of longer-lived innate lymphoid cells. Since a continuing response is associated with allergic inflammation, it is important for us to understand how these cells are turned off,” explained Moro.
A key finding of the study is that these innate lymphoid cells can be shut off by certain cytokine chemicals, that is, interferon-beta, gamma and interleukin-27, to end the immune response and ensure that the inflammation does not last.
In addition, the scientists helped clear up a mystery about these cells by showing that they do not circulate to tissues that require an immune response but are actually located in the tissues, and are only turned on when a threat is detected.
“This shows,” said Moro, “that the response is mounted in a very locally specific way. This may be another way for the body to prevent the lasting inflammation that can be associated with the response.”
The findings may help scientists understand how the type 2 innate response changes to be both beneficial and harmful, according to Shigeo Koyasu, group director of the Laboratory for Immune Cell Systems, who led the group.
“Learning how these cells are activated and inactivated can give us clues for understanding and treating how the body reacts to such infections,” said Koyasu.
Koyasu said that scientists are beginning to gain insights into the innate immune response, which was previously thought to be simpler than our understanding today.
“I hope that our work will encourage researchers to look for similar regulatory mechanisms in type 1 and type 3 innate immune responses as well, as this will help us to gain a broader understanding of the complexity of our immune response,” said Koyasu.