October 17, 2007

New research sheds light on how allergic
response changes with age
Study suggests how body 'learns' over time to tolerate certain allergens, as dendritic
cells become hypersensitive with exposure
RIKEN research reported this week suggests why some people develop new or different
allergies and even adult-onset asthma as they grow older.
The findings by a group of researchers from RIKEN, Tokyo University and Musashino
University are to be published soon in the peer-reviewed journal of the American
Academy of Allergy, Asthma & Immunology. RIKEN is a leading Japanese researchinstitute based in the city of Wako in Saitama Prefecture, near Tokyo.
Immature regulatory dendritic cells, the 'sentinels' of the body's immune system, cantrigger violent responses to allergens when the cells are still developing, but may lateract to suppress those responses as the cells mature. This gives clues as to theunderlying mechanism of how the body 'learns' over time to tolerate certain allergens.
Allergens such as pollen, cat dander and house dust are increasingly the bane of allergy
sufferers. Allergens can also bring on asthma attacks that affect up to one in four urban
children in developed countries. In the worst attacks, the mucus membranes of thehuman body react violently when cued by the regulatory dendritic cells, severely
restricting air passages and inflaming tissues in the lungs, nose and eyes. In essence,
the body turns against itself in an effort to expel the offending airborne invaders throughsneezing, coughing and upper respiratory tract congestion.
Medical science has largely been at a loss about the actual mechanism behind theseattacks, though direct evidence of the malady itself is as close as the nearest cedar tree,
ragweed plant or fuzzy pet. What Dr. Fujita and his RIKEN-supported team have seen,
through cellular-level studies involving mice specially bred for sensitivity to specificallergen chemical compounds, is that there is more going on than was thought.
A main focus of the research was on the action of dendritic cells that exist in thelymphatic system and peripheral tissues. These cells act as sentinels against bacteria
and other alien invaders, including ragweed and other types of pollen. Activation of theimmune system requires that an incipient invasion first be detected. This is carried out
by tissue macrophages, which alert the body's innate immunity, and by dendritic cells,
which alert the adaptive immune system. As part of the adaptive function, the body may
not react to the first series of exposures but eventually becomes acutely sensitized tolater exposures, thanks to those otherwise-helpful dendritic cells.
The researchers found through chemical indications at the cellular level that theanti-allergen response engages differently for immunized mice compared tonon-immunized mice that had not previously been exposed to a specific allergenchemical compound. Controlling for the development stage of the dendritic cells, theyrecognized that the typical reaction of the cell was to send signals to fight off an allergen
if the cell was immature, but could later tolerate the allergen after the dendritic cell hadmatured.
How this phenomenon might be manipulated to prevent the onset of certain types ofasthma is one focus of subsequent research on what the authors say are promising'novel approaches' on how to keep the body from turning on itself as part of an immune
system gone awry.
Original work:
Fujita, S., Yamashita, N., Ishii, Y., Sato, Y., Sato, K., Eizumi, K., Fukaya, T., Nozawa, R.,
Takamoto, Y., Yamashita, N., Taniguchi, M. and Sato, K. Regulatory dendritic cells
protect against allergic airway inflammation in a murine asthmatic model. Journal ofAllergy Clinical Immunology, published online on Oct 17, 2007

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