Dying cells trigger immunity

May 30, 2014
Figure 1: DNA (red) is taken up inside naive T cells (green), leading to their activation and differentiation into T helper type 2 (Th2) cells. Credit: T. Imanishi et al

The immune system produces various types of immune cells—some are pre-programmed to target pathogens that the immune system has previously encountered, while others are 'naive' and retain the ability to mature or differentiate into specific cell types to target new invaders. Some of the triggers of this differentiation, however, remain poorly understood.

Takashi Saito, Takayuki Imanishi and colleagues from the Laboratory for Cell Signaling at the RIKEN Center for Integrative Medical Sciences have now led an international team of researchers that has found that nucleic acids, such as DNA and RNA, released from dying cells can trigger naive immune T cells to differentiate into T helper type 2 (Th2) cells.

The researchers performed a series of experiments where naive T cells were cultured with different kinds of nucleic acid species to induce T-cell activation. They found that certain classes of nucleic acids that tended to interact with other nucleic acids were more effective at activating T cells (Fig. 1), suggesting that these structural interactions enhance nucleic acid stability and uptake. Nucleic acids bound to various antimicrobial peptides and proteins—typical of the nucleic acids released by dying cells—also tended to promote T-cell activation, indicating that activation occurs at sites of inflammation or infection.

"Nucleic acids have previously been shown to be recognized by innate immune cells that present antigens to stimulate T cells," explains Saito, "but this study clarifies that T cells are directly activated by the nucleic acids themselves."

In many types of immune cells, nucleic acids bind to a class of proteins called Toll-like receptors (TLRs, which sense pathogen-associated molecular patterns to initiate innate responses and help regulate T cell-mediated adaptive immune responses. The researchers were surprised to find that TLRs did not seem to play a role in nucleic-acid-driven T-cell differentiation. 

Instead, the researchers found that exposure to nucleic acids induced in the naive T cells the expression of a transcription factor that is known to specifically drive Th2 maturation. This was evidenced by the secretion of proteins characteristic of Th2 cells when naive T cells were cultured with nucleic acids.

Th2 drive the immune response against parasitic worms and serve a key role in triggering allergic reactions. The findings therefore suggest that blocking the ability of to induce Th2 maturation could be a promising possible therapeutic approach to reducing the severity of allergies in humans.

Explore further: Who goes there? Novel complex senses viral infection

More information: Imanishi, T., Ishihara, C., Badr, M. E. S. G., Hashimoto-Tane, A., Kimura, Y., Kawai, T., Takeuchi, O., Ishii, K. J., Taniguchi, S., Noda, T. et al. "Nucleic acid sensing by T cells initiates Th2 cell differentiation." Nature Communications 5, 3566 (2014). DOI: 10.1038/ncomms4566.

Related Stories

Who goes there? Novel complex senses viral infection

June 23, 2011

Double-stranded (ds) RNA viruses are a diverse group of viruses that include rotaviruses, a common cause of gastroenteritis. The ability of the immune system to detect and destroy viruses is critical for human health and ...

Recommended for you

Snapshot turns T cell immunology on its head

October 6, 2015

Challenging a universally accepted, longstanding consensus in the field of immunity requires hard evidence. New research from the Australian Research Council Centre of excellence in advanced Molecular imaging has shown the ...

Four gut bacteria decrease asthma risk in infants

September 30, 2015

New research by scientists at UBC and BC Children's Hospital finds that infants can be protected from getting asthma if they acquire four types of gut bacteria by three months of age. More than 300 families from across Canada ...

Flu infection reveals many paths to immune response

September 28, 2015

A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological ...

Immune cells may help fight against obesity

September 15, 2015

While a healthy lifestyle and "good genes" are known to help prevent obesity, new research published on September 15 in Immunity indicates that certain aspects of the immune system may also play an important role. In the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.