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Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production.

Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K - J. Exp. Med. (1997)

Bottom Line: When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells.These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes.These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lcohn@biomed.med.yale.edu

ABSTRACT
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

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Mucus production  and airway inflammation in mice  after transfer of cells to IL-4 −/−  recipient mice. IL-4 −/− mice  received transfer of OVA-specific IL-4 +/+ or IL-4 −/−  Th2 cells and exposure to TNF-α  and 7 d of inhaled OVA. HMI  was performed on lung sections  stained with DPAS. Mean HMI  (±SEM) is shown. (n = 3–4  mice per group). One experiment is shown and is representative of two experiments.
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Figure 8: Mucus production and airway inflammation in mice after transfer of cells to IL-4 −/− recipient mice. IL-4 −/− mice received transfer of OVA-specific IL-4 +/+ or IL-4 −/− Th2 cells and exposure to TNF-α and 7 d of inhaled OVA. HMI was performed on lung sections stained with DPAS. Mean HMI (±SEM) is shown. (n = 3–4 mice per group). One experiment is shown and is representative of two experiments.

Mentions: These results show clearly that donor IL-4–deficient Th2 cells can stimulate mucus production in the airway. However, to rule out a possible role of endogenous IL-4 secretion in mucus production, we transferred IL-4 +/+ and IL-4 −/− Th2 cells into IL-4–deficient recipient mice. Mice were exposed to TNF-α and then aerosolized OVA for 7 d. As seen in Fig. 8, there was persistent induction of mucus in the airway epithelium in mice that received IL-4 −/− Th2 cells in the absence of any recipient IL-4. Clearly, IL-4 secreted by CD4 T cells or by other cells recruited in the inflammatory process is not necessary to stimulate mucus production in the airway epithelium.


Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production.

Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K - J. Exp. Med. (1997)

Mucus production  and airway inflammation in mice  after transfer of cells to IL-4 −/−  recipient mice. IL-4 −/− mice  received transfer of OVA-specific IL-4 +/+ or IL-4 −/−  Th2 cells and exposure to TNF-α  and 7 d of inhaled OVA. HMI  was performed on lung sections  stained with DPAS. Mean HMI  (±SEM) is shown. (n = 3–4  mice per group). One experiment is shown and is representative of two experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199146&req=5

Figure 8: Mucus production and airway inflammation in mice after transfer of cells to IL-4 −/− recipient mice. IL-4 −/− mice received transfer of OVA-specific IL-4 +/+ or IL-4 −/− Th2 cells and exposure to TNF-α and 7 d of inhaled OVA. HMI was performed on lung sections stained with DPAS. Mean HMI (±SEM) is shown. (n = 3–4 mice per group). One experiment is shown and is representative of two experiments.
Mentions: These results show clearly that donor IL-4–deficient Th2 cells can stimulate mucus production in the airway. However, to rule out a possible role of endogenous IL-4 secretion in mucus production, we transferred IL-4 +/+ and IL-4 −/− Th2 cells into IL-4–deficient recipient mice. Mice were exposed to TNF-α and then aerosolized OVA for 7 d. As seen in Fig. 8, there was persistent induction of mucus in the airway epithelium in mice that received IL-4 −/− Th2 cells in the absence of any recipient IL-4. Clearly, IL-4 secreted by CD4 T cells or by other cells recruited in the inflammatory process is not necessary to stimulate mucus production in the airway epithelium.

Bottom Line: When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells.These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes.These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lcohn@biomed.med.yale.edu

ABSTRACT
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

Show MeSH
Related in: MedlinePlus