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BYU chemists team with U. of Chicago to better describe immune response

As part of a team of scientists, a Brigham Young University professor and his graduate students helped discover a new key to how the body regulates the immune system.

The finding has important implications in understanding how the body responds to threats from bacterial pathogens. The work may also shed light on the roots of chronic autoimmune conditions like multiple sclerosis, lupus and rheumatoid arthritis.

To be published Thursday, March 24, in the prestigious scientific journal "Nature," the research revolves around special cells called natural killer T cells, which act like switches in the body, determining whether to unleash an aggressive, inflammatory immune system response or to enter into a "surveillance" mode.

"Natural killer T cells are the 'shepherds' of the T cell 'sheep,' a category of white blood cells that are crucial to a healthy immune system," says BYU chemistry professor Paul B. Savage. "Knowing what types of molecules stimulate these natural killer T cells is to better understand how the body regulates immunity. "

In "Nature," researchers, including BYU's Savage, report that they have found that natural killer T cells can be directly switched to attack mode by some types of bacteria.

"So something your body doesn't make naturally, something that comes in from the outside environment, can play a direct role in the way your immune system responds," says Savage. "In other words, bacterial infections can directly influence this immunological switch."

In December, Savage and other scientists reported in the journal "Science" the identity and description of another of the previously elusive keys that trigger natural killer T cell – an antigen produced naturally by the body that can trigger immune response.

Also in the "Nature" paper, researchers report a third way killer T cells can be mobilized to action – via indirect stimulation. Another key player in the immune system called a macrophage, a type of white blood cell that surrounds and kills microorganisms, can send a signal from afar to activate T cells. If, at the same time, the body's natural antigen is being presented to the natural killer T cell, the cell will promote the attack mode of immune response to fight foreign invaders.

Armed with this knowledge, Savage, his fellow researchers and other scientists can further refine the understanding of the human immune system and potentially influence immune responses to avoid problems associated with chronic autoimmune diseases and to better fight off infections. Based on these breakthroughs it is likely that in the future new medicines will be developed to curb overactive immune systems or boost deficient ones, Savage hopes.

"Basically, these results mean we better understand how the body's immune system works – what ramps it up and what turns it down," says Savage. "This discovery opens up a whole new branch of immunology."

Savage and three of his graduate students, Randall Goff, Ning Yin and Ying Gao, are organic chemists in the research team who designed and synthesized antigens.

In addition to the BYU team, other authors on the paper are Jochen Mattner, Kristin L. DeBord, Dapeng Zhou, Pierre Saint-Mezzard, Vivien Wang, Olaf Schneewind and Albert Bendelac at the University of Chicago; Nahed Ismail and David Walker of the University of Texas Medical Branch; and Carlos Cantu III, Kasper Hoebe, Bruce Beutler and Luc Teyton of the Scripps Research Institute.

Writer: Grant Madsen and Michael Smart