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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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Related in: MedlinePlus

Mucus staining in  airways of mice after transfer of  Th1, Th2, or naive (N) CD4 T  cells and exposure to inhaled  OVA. An Histologic Mucus Index (HMI) was performed on  lung sections stained with DPAS.  Mean HMI (±SEM) is shown (n  = 4 mice per group). One experiment is shown and is representative of three experiments.  Statistical significance was determined by unpaired Student's t  test. *P <0.0001, Th1 vs. Th2.
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Figure 5: Mucus staining in airways of mice after transfer of Th1, Th2, or naive (N) CD4 T cells and exposure to inhaled OVA. An Histologic Mucus Index (HMI) was performed on lung sections stained with DPAS. Mean HMI (±SEM) is shown (n = 4 mice per group). One experiment is shown and is representative of three experiments. Statistical significance was determined by unpaired Student's t test. *P <0.0001, Th1 vs. Th2.

Mentions: Bronchial epithelial cells in mice that received OVA-specific Th2 cells and inhaled OVA showed hyperplasia and extensive DPAS positive staining indicating the presence of mucin collections (Fig. 2 B3). These findings were most striking in the central airways, although peripheral airways were also involved. Histological sections also showed increased amounts of mucus within the airway lumena of mice that received Th2 cells and aerosolized OVA. The material also stained positive for mucicarmine and alcian blue (data not shown). Mice that received Th1 cells and inhaled OVA had minimal to absent mucus staining (Fig. 2 A3). An HMI performed on lung sections from mice that received Th2 cells and inhaled OVA showed that 65% of airway epithelial cells were mucinous, while mice that received Th1 cells and inhaled OVA or naive CD4 T cells and inhaled OVA had <5% of mucinous cells in the airways (Fig. 5).


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 staining in  airways of mice after transfer of  Th1, Th2, or naive (N) CD4 T  cells and exposure to inhaled  OVA. An Histologic Mucus Index (HMI) was performed on  lung sections stained with DPAS.  Mean HMI (±SEM) is shown (n  = 4 mice per group). One experiment is shown and is representative of three experiments.  Statistical significance was determined by unpaired Student's t  test. *P <0.0001, Th1 vs. Th2.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Mucus staining in airways of mice after transfer of Th1, Th2, or naive (N) CD4 T cells and exposure to inhaled OVA. An Histologic Mucus Index (HMI) was performed on lung sections stained with DPAS. Mean HMI (±SEM) is shown (n = 4 mice per group). One experiment is shown and is representative of three experiments. Statistical significance was determined by unpaired Student's t test. *P <0.0001, Th1 vs. Th2.
Mentions: Bronchial epithelial cells in mice that received OVA-specific Th2 cells and inhaled OVA showed hyperplasia and extensive DPAS positive staining indicating the presence of mucin collections (Fig. 2 B3). These findings were most striking in the central airways, although peripheral airways were also involved. Histological sections also showed increased amounts of mucus within the airway lumena of mice that received Th2 cells and aerosolized OVA. The material also stained positive for mucicarmine and alcian blue (data not shown). Mice that received Th1 cells and inhaled OVA had minimal to absent mucus staining (Fig. 2 A3). An HMI performed on lung sections from mice that received Th2 cells and inhaled OVA showed that 65% of airway epithelial cells were mucinous, while mice that received Th1 cells and inhaled OVA or naive CD4 T cells and inhaled OVA had <5% of mucinous cells in the airways (Fig. 5).

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