Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation

Randolph, David A.; Stephens, Robin; Carruthers, Christopher; Chaplin, David

doi:10.1172/jci7631

Cited by 289 publications

(224 citation statements)

References 56 publications

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“…50 It should be pointed out that Th1 cells can exacerbate airway inflammation. 51,52 Thus, our observed overall phenotype of gal3 Ϫ/Ϫ mice may reveal that reduction in the Th2 response exceeds any increase in the Th1 response.…”

Section: Discussionmentioning

confidence: 89%

Critical Role for Galectin-3 in Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma

Zuberi

Hsu

Kalaycı

et al. 2004

The American Journal of Pathology

160

154

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Galectin-3 is a member of a ␤-galactoside-binding animal lectin family. Previous in vitro studies have demonstrated that galectin-3 is involved in a number of activities; however, the roles of this lectin in physiological and pathological processes in vivo remain to be elucidated. Herein, we show, in a murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from OVAchallenged mice contained significantly higher levels of galectin-3 compared to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the major cell type that contained galectin-3. We investigated the role of galectin-3 in the allergic airway response by comparing galectin-3-deficient (gal3 ؊/؊ ) mice and wild-type (gal3 ؉/؉ ) mice. OVA-sensitized gal3 ؊/؊ mice developed fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge compared to similarly treated gal3 ؉/؉ mice. In addition, the OVA-sensitized gal3 ؊/؊ mice developed significantly less airway hyperresponsiveness after airway OVA challenge compared to gal3 ؉/؉ mice. Finally, gal3 ؊/؊ mice developed a lower Th2 response, but a higher Th1 response, suggesting that galectin-3 regulates the Th1/Th2 response. We conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease.

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Section: Discussionmentioning

confidence: 89%

Critical Role for Galectin-3 in Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma

Zuberi

Hsu

Kalaycı

et al. 2004

The American Journal of Pathology

160

154

View full text Add to dashboard Cite

show abstract

“…In agreement with this finding, other authors have suggested that the immune regulation of asthma and allergic diseases is much more complex than a mere imbalance between Th1 and Th2 cells. In particular, Th2 cell-induced inflammation could not be diminished in an adoptive transfer model with antigen-specific Th1 cells, which did effectively reduce airway mucus production and eosinophilia, when they were given in excess [32,33].…”

Section: Discussionmentioning

confidence: 93%

Exacerbated Th2‐mediated airway inflammation and hyperresponsiveness in autoimmune diabetes‐prone NOD mice: a critical role for CD1d‐dependent NKT cells

et al. 2004

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The NOD mouse has proved to be a relevant model of insulin-dependent diabetes mellitus, closely resembling the human disease. However, it is unknown whether this strain presents a general bias toward Th1-mediated autoimmunity or remains capable of mounting complete Th2-mediated responses. Here, we show that NOD mice have the capacity to develop a typical Th2-mediated disease, namely experimental allergic asthma. In contrast to what might have been expected, they even developed a stronger Th2-mediated pulmonary inflammatory response than BALB/c mice, a strain that shows a typical Th2 bias in this model. Thus, after allergen sensitization and intra-nasal challenge, the typical features of experimental asthma were exacerbated in NOD mice, including enhanced bronchopulmonary responsiveness, mucus production and eosinophilic inflammation in the lungs as well as specific IgE titers in serum. These hallmarks of allergic asthma were associated with increased IL-4, IL-5, IL-13 and eotaxin production in the lungs, as compared with BALB/c mice. Notwithstanding their quantitative and functional defect in NOD mice, CD1d-dependent NKT cells contribute to aggravate the disease, since in OVA-immunized CD1d -/-NOD mice, which are deficient in this particular T cell subset, airway eosinophilia was clearly diminished relative to NOD littermates. This is the first evidence that autoimmune diabetesprone NOD mice can also give rise to enhanced Th2-mediated responses and might thus provide a useful model for the study of common genetic and cellular components, including NKT cells that contribute to both asthma and type 1 diabetes.

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“…Immune deviation strategies have been proposed for other Th2-mediated diseases including allergy and asthma. 7,[37][38][39][40] The results presented here suggest that the ultimate success of these strategies will rely not only on the successful establishment of a type-1-dominant response, but also on the simultaneous and efficient activation of NOS-2 expression in downstream effector populations. Indeed, it is intriguing to speculate that the previously reported inability of Th1 cells to modulate Th2-mediated inflammation 38,39 may be due entirely to the inefficient activation of NOS-2 at sites of inflammation.…”

Section: Discussionmentioning

confidence: 99%

NOS-2 Mediates the Protective Anti-Inflammatory and Antifibrotic Effects of the Th1-Inducing Adjuvant, IL-12, in a Th2 Model of Granulomatous Disease

Hesse

Cheever

Janković

et al. 2000

The American Journal of Pathology

110

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Mice sensitized with Schistosoma mansoni eggs and IL-12 develop liver granulomas, on subsequent infection, which are smaller and less fibrotic than those in nonsensitized mice. The protective response is accompanied by a shift in the type-2 cytokine profile to one dominated by type-1 cytokines. The deviated response is associated with marked increases in inducible nitric oxide synthase (NOS-2) activity. Here, we demonstrate, by using NOS-2-deficient mice, that the anti-inflammatory and anti-fibrotic effects of the type-1 response are completely NOS-2-dependent. Strikingly, despite developing a polarized type-1 cytokine response that was similar in magnitude, the egg/IL-12-sensitized NOS-deficient mice developed granulomas 8 times larger than WT mice did. There was also no decrease in hepatic fibrosis in the sensitized mutant animals. Interferon-␥-deficient mice failed to exhibit the exacerbated inflammatory response, despite displaying a marked deficiency in nitric oxide production. However, immune deviation was unsuccessful in the latter animals, which suggested that the increase in inflammation in NOS-deficient mice resulted from a polarized but nitric oxidedeficient type-1 response. These results reveal a beneficial role for NOS-2 in the regulation of inflammation and suggest that the ultimate success of Th2-to-Th1 immune deviation strategies will rely on the efficient activation of NOS-2 expression in downstream effector cells.

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Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation

Cited by 289 publications

References 56 publications

Critical Role for Galectin-3 in Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma

Critical Role for Galectin-3 in Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma

Exacerbated Th2‐mediated airway inflammation and hyperresponsiveness in autoimmune diabetes‐prone NOD mice: a critical role for CD1d‐dependent NKT cells

NOS-2 Mediates the Protective Anti-Inflammatory and Antifibrotic Effects of the Th1-Inducing Adjuvant, IL-12, in a Th2 Model of Granulomatous Disease

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