Consortium researchers will explore the possibility that allergic asthma results from release by immune white blood cells of an inflammatory substance that directs immune T cells to attack lung tissue.
Asthma is characterized by infiltration and accumulation in inflamed lungs of a specific type of memory T cells (specific types of CD4+T cells) and “eosinophils,” which are immune white blood cells that produce inflammation. In people with asthma, these immune T cells are thought to become overly sensitive to otherwise harmless agents, remember the allergen, and react whenever the allergen is encountered. The T cells maintain chronic allergic inflammation and generate rapid inflammation whenever asthma sufferers are exposed to allergens. Scientists have little understanding, however, of the nature of these memory T cells in humans and how they are regulated and maintained.
The King's College and M.D. Anderson Center researchers recently discovered that a substance (called TSLP), found in cells in the lining of the lung, activates immune dendritic cells (DCs) during allergic inflammation. The DCs stimulate the memory T cells to respond to the allergen and to proliferate. TSLP, they suggest, may constitute the missing link in this immunological cascade that stimulates and maintains memory T activation in asthma. Additionally, the M.D. Anderson researchers found that eosinophils appear to produce the inflammation-producing substance, an immune “cytokine” called IL-25. This raises the possibility that eosinophil production of IL-25 may exert a critical role in maintaining the allergen-specific memory T cells in allergic inflammation, providing a feedback loop for further activation of these memory T cells. This suggestion turns current thinking upside down. Instead of eosinophils being the consequence of the memory T cell actions, the eosinophils would actually be driving the memory T cells through production of IL-25. The researchers will combine their expertise in immunology (M.D. Anderson) and molecular immunopathology (Kings College) to test this hypothesis in laboratory studies of tissue obtained from people with asthma.
Significance: If the research demonstrates that interaction between immune eosinophils and memory T cells occurs in asthma via eosinophil production of the inflammatory cytokine IL-25, the findings may lead to novel means to block this inflammatory cytokine or its effect on immune T cells.