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

Kang HS, Blink SE, Chin RK, Lee Y, Kim O, Weinstock J, Waldschmidt T, Conrad D, Chen B, Solway J, Sperling AI, Fu YX - J. Exp. Med. (2003)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.

ABSTRACT
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.

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Related in: MedlinePlus

LT is required for IgE production. The sera from various 12–16-wk-old LTα−/− mice (n = 9) were collected, and total IgE concentration was measured by ELISA. Data represent the mean ± SE.
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fig2: LT is required for IgE production. The sera from various 12–16-wk-old LTα−/− mice (n = 9) were collected, and total IgE concentration was measured by ELISA. Data represent the mean ± SE.

Mentions: Increased airway inflammation is often associated with elevated serum IgE concentrations. Despite the increased airway inflammation in naive LTα−/− mice, unexpectedly we found IgE concentrations reduced to nearly undetectable levels (Fig. 2) . LTα−/− mice lack both soluble and membrane LT. Either membrane or soluble LT could be required for IgE production; therefore, the sera from LTβ−/− mice were collected. These mice, which lack only the membrane form of LT, also have low IgE levels. To better define the receptor involvement, serum from LTβR−/− mice was collected and found to share the IgE defect observed in LTα−/− mice, thus identifying a new ligand and receptor pair required for IgE production. Interestingly, TNF, another closely related cytokine that shares the same receptors as soluble LT, is dispensable for IgE production (Fig. 2). These data revealed the presence of membrane LT and its receptor, LTβR−/−, are critical for IgE production.


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

Kang HS, Blink SE, Chin RK, Lee Y, Kim O, Weinstock J, Waldschmidt T, Conrad D, Chen B, Solway J, Sperling AI, Fu YX - J. Exp. Med. (2003)

LT is required for IgE production. The sera from various 12–16-wk-old LTα−/− mice (n = 9) were collected, and total IgE concentration was measured by ELISA. Data represent the mean ± SE.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194142&req=5

fig2: LT is required for IgE production. The sera from various 12–16-wk-old LTα−/− mice (n = 9) were collected, and total IgE concentration was measured by ELISA. Data represent the mean ± SE.
Mentions: Increased airway inflammation is often associated with elevated serum IgE concentrations. Despite the increased airway inflammation in naive LTα−/− mice, unexpectedly we found IgE concentrations reduced to nearly undetectable levels (Fig. 2) . LTα−/− mice lack both soluble and membrane LT. Either membrane or soluble LT could be required for IgE production; therefore, the sera from LTβ−/− mice were collected. These mice, which lack only the membrane form of LT, also have low IgE levels. To better define the receptor involvement, serum from LTβR−/− mice was collected and found to share the IgE defect observed in LTα−/− mice, thus identifying a new ligand and receptor pair required for IgE production. Interestingly, TNF, another closely related cytokine that shares the same receptors as soluble LT, is dispensable for IgE production (Fig. 2). These data revealed the presence of membrane LT and its receptor, LTβR−/−, are critical for IgE production.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus