Signaling pathways critical for allergic airway inflammation.
OBJECTIVE
Activated mast cells, basophils, and CD4 helper T cells have critical roles in allergic inflammation. Therefore, devising ways to specifically inhibit these cells will likely be useful for controlling allergic inflammation. We summarize recent findings regarding the role of mast cells and basophils in allergic responses and the regulation of signaling pathways downstream of the IgE receptor, the chief inducer of mast cell and basophil activation. We also highlight studies addressing the roles of the protein tyrosine kinases Zap-70 and Itk in immune system development and in the regulation of CD4 helper T cell responses.


RESULTS
Recent work has demonstrated that mast cell function is unexpectedly diverse and that basophils have a more prominent role in Th2-type immune responses than previously appreciated. Biochemical analysis of the IgE receptor signaling pathway has led to insights regarding the roles of phosphatases and other enzymes in this process. Studies of Zap-70 and Itk have helped to define the potential outcomes and complications of inhibiting these enzymes in order to suppress allergic inflammation.


CONCLUSIONS
Analysis of genetically engineered mice and biochemical studies continue to help unravel the molecular pathways that drive allergic inflammatory reactions. The knowledge acquired may lead to novel approaches for suppressing allergic inflammation.
Colgan
John D
JD
Department of Internal Medicine, University of Iowa, Iowa City, USA. john-colgan@uiowa.edu
Hankel
Isaiah L
IL
D000818:Animals; D030801:Animals, Genetically Modified; D001491:Basophils / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D007165:Immunosuppression Therapy; D007249:Inflammation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology / Q000378:metabolism*
D017455:Receptors, IgE; C489300:LTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase