thor Warren Pear, MD, PhD, Associate Professor of Pathology and Laboratory Medicine, was one of the original discoverers of the role of Notch signaling in T-cell development. Notch activates gene transcription in the nucleus of cells, and depending on the biochemical context, it turns certain pathways on and others off. "The potential importance of our study is that it shows that Notch signaling specifically influences Th2 immunity in a live animal when challenged with a pathogen, suggesting that drugs that inhibit Notch may be useful for treating diseases associated with a pathological Th2 response, such as asthma," says Pear. He is also a member of Penn's Abramson Family Cancer Research Institute and The Institute for Medicine and Engineering.

Helper T cells fight many types of infectious diseases and are also the cells that regulate tolerance to self and the molecules that cause the pathogenesis of such inflammatory diseases as arthritis, inflammatory bowel disease, and asthma. Antigen-presenting cells take up pathogens and migrate to the spleen or lymph nodes, where they instruct immature T cells how to differentiate into Th1 or Th2 helper T cells, killer T cells, or other types of immune system cells.

Some of the factors that signal a T cell to become Th1 or Th2 cells are well characterized, but some are not. "The role of Notch in that decision-making has been controversial," says co-author Terry Fang, a graduate student in Penn's Immunology Program. "And this paper weighs in on this." Some studies suggest that Notch is important for the Th1 pathway, others suggest both Th1 and Th2. This study suggests that there's a specific requirement for Notch in Th2 differentiation only.

The specificity of Notch in regulating T-cell function is highlighted in this study. "Mice lacking Notch failed to control infection with a pathogen requiring a Th2 response, demonstrating that Notch is a critical regulator of this response," adds co-author David
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
17-Oct-2005

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