Lymphotoxin is required for maintaining physiological levels of serum IgE that minimizes Th1-mediated airway inflammation

Although elevated levels of IgE in asthmatic patients are strongly associated with lung infiltration by activated T helper (Th) 2 cells, the physiological role of immunoglobulin E (IgE) in the airway remains largely undefined. Lymphotoxin-deficient alpha (LTalpha(-/-)) mice exhibit increased airway inflammation, paradoxically accompanied by diminished levels of IgE and reduced airway hyper-responsiveness in response to both environmental and induced antigen challenge. The severe lung inflammation in LTalpha(-/-) mice is Th1 in nature and can be alleviated by IgE reconstitution. Conversely, depletion of IgE in wild-type mice recapitulates the lung pathologies of LTalpha(-/-) mice. Therefore, this work has revealed that lymphotoxin is essential for IgE production, and a physiological role of IgE in the airway may consist of maintaining the balance of Th1 and Th2 responses to prevent aberrant inflammation.