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 hyperresponsiveness 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.
Kang
Hyung-Sik
HS
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Blink
Sarah E
SE
Chin
Robert K
RK
Lee
Youjin
Y
Kim
Oliver
O
Weinstock
Joel
J
Waldschmidt
Thomas
T
Conrad
Daniel
D
Chen
Bohao
B
Solway
Julian
J
Sperling
Anne I
AI
Fu
Yang-Xin
YX
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000097:blood* / Q000172:deficiency; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015656:Respiratory Mechanics; D018417:Th1 Cells / Q000276:immunology*
D008233:Lymphotoxin-alpha; D007073:Immunoglobulin E