last updated April 2013
Understanding the development of allergic inflammation advances from the identification of a crucial protein
Allergic responses can be triggered by the inflammatory cytokine interleukin-9 (IL-9), which is secreted by a recently identified subset of T cells called TH9 cells. Now, a research team from the United States and Australia, led by Mark Kaplan from the Indiana University School of Medicine, has identified that a transcription factor protein called PU.1 is needed for the development of these cells1.
The researchers found that T cells from PU.1-deficient mice secreted less IL-9 than T cells from normal mice. When they forced expression of PU.1 in T cells in cell culture, they noted an increase in IL-9 expression. PU.1 seemed to act by binding directly to the IL-9 gene in the genomic DNA, and inducing the expression of IL-9.
In PU.1-deficient mice, the researchers observed less allergic airway inflammation in response to antigen exposure, and this correlated with less IL-9 expression in their T cells. Alterations in levels of IL-9 also seemed to affect allergic responses in humans: in young children with allergies, the researchers found increased expression of IL-9, which may have come from TH9 cells. Moreover, blocking PU.1 expression in human T cells decreased IL-9 production.
Blocking production of PU.1 and IL-9 may provide therapies to prevent or treat allergic responses, the team suggests.