T cell activation, from atopy to asthma: more a paradox than a paradigm

Biaze, M. El; Boniface, S.; Koscher, V.; Mamessier, Émilie; Dupuy, P; Milhe, F.; Ramadour, M.; Vervloët, D.; Magnan, A.

doi:10.1034/j.1398-9995.2003.00282.x

Cited by 87 publications

(56 citation statements)

References 102 publications

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“…Relevant for the inception of atopy, it only partially explains the inflammation present in asthma and atopic dermatitis. In asthma and atopic dermatitis, a type 1 component of inflammation is present, which is related to symptoms [32,33,34,35]. An additional explanation is that the cellular threshold for IFN-γ and TNF-α is rather lower than for type 2 cytokines.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis and Loss of Adhesion of Bronchial Epithelial Cells in Asthma

Trautmann¹,

Krüger²,

Akdiş³

et al. 2005

Int Arch Allergy Immunol

112

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Background: Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-γ and TNF-α. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines. Methods: Bronchial EC, cultured and exposed to IFN-γ and TNF-α, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules. Results: We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of β₁-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation. Conclusions: Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC.

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Section: Discussionmentioning

confidence: 99%

Apoptosis and Loss of Adhesion of Bronchial Epithelial Cells in Asthma

Trautmann¹,

Krüger²,

Akdiş³

et al. 2005

Int Arch Allergy Immunol

112

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“…Therefore, the dramatic increase in the expression of Th2 cytokines does not occur at the expense of the expression of Th1 cytokines, but both responses are present. Such a mixed cytokine response is often present in asthmatic patients, and models in mice suggest that complex interactions between Th1 and Th2 cytokines can augment disease severity and lead to increased lung injury and fibrosis (15)(16)(17). Chronic models of lung inflammation will be used to examine the effect of TIM-2 deficiency on the extent of airway remodeling and airway resistance.…”

Section: Discussionmentioning

confidence: 99%

T Cell, Ig Domain, Mucin Domain-2 Gene-Deficient Mice Reveal a Novel Mechanism for the Regulation of Th2 Immune Responses and Airway Inflammation

Rennert

Ichimura

Sizing

et al. 2006

The Journal of Immunology

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The development of asthma and other atopic diseases is influenced by cytokines produced by Th2 effector T cells. How effector T cell responses are regulated once these cell populations are established remains unclear. The recently described T cell and airway phenotype regulator locus, containing the T cell, Ig domain, mucin domain (TIM) genes, is genetically associated with Th2 cytokine production and Th2-dependent immune responses. In this study, we report the phenotype of the TIM-2 gene-deficient mouse, and demonstrate exacerbated lung inflammation in an airway atopic response model. Immune responses in the TIM-2-deficient mouse reveal disregulated expression of Th2 cytokines, and adoptive transfer experiments show that the T cell compartment is responsible for the heightened inflammatory phenotype. These studies show that TIM-2 is a novel and critical regulator of effector T cell activity.

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“…Simplistically, the uncontrolled inflammatory response, accompanied by the overexpression of CLCA protein, is thought to occur through a dysregulation between type 1 helper T (Th1) and type 2 helper T (Th2) cell immune responses to allergens (10,27,47,90,134,159,192). The Th1-immune response involving interleukin (IL)-2 and interferon (IFN)-␥ cytokines is seen as a cell-mediated response associated with disease in situations of poor hygiene or infection with Mycobacterium tuberculosis, measles virus, or hepatitis A virus (21,127,130,167,171).…”

Section: Asthma and The Genesis Of Its Mediatorsmentioning

confidence: 99%

Structure and Function of CLCA Proteins

Loewen¹,

Forsyth²

2005

Physiological Reviews

119

126

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CLCA proteins were discovered in bovine trachea and named for a calcium-dependent chloride conductance found in trachea and in other secretory epithelial tissues. At least four closely located gene loci in the mouse and the human code for independent isoforms of CLCA proteins. Full-length CLCA proteins have an unprocessed mass ratio of ∼100 kDa. Three of the four human loci code for the synthesis of membrane-associated proteins. CLCA proteins affect chloride conductance, epithelial secretion, cell-cell adhesion, apoptosis, cell cycle control, mucus production in asthma, and blood pressure. There is a structural and probable functional divergence between CLCA isoforms containing or not containing β4-integrin binding domains. Cell cycle control and tumor metastasis are affected by isoforms with the binding domains. These isoforms are expressed prominently in smooth muscle, in some endothelial cells, in the central nervous system, and also in secretory epithelial cells. The isoform with disrupted β4-integrin binding (hCLCA1, pCLCA1, mCLCA3) alters epithelial mucus secretion and ion transport processes. It is preferentially expressed in secretory epithelial tissues including trachea and small intestine. Chloride conductance is affected by the expression of several CLCA proteins. However, the dependence of the resulting electrical signature on the expression system rather than the CLCA protein suggests that these proteins are not independent Ca2+-dependent chloride channels, but may contribute to the activity of chloride channels formed by, or in conjunction with, other proteins.

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T cell activation, from atopy to asthma: more a paradox than a paradigm

Cited by 87 publications

References 102 publications

Apoptosis and Loss of Adhesion of Bronchial Epithelial Cells in Asthma

Apoptosis and Loss of Adhesion of Bronchial Epithelial Cells in Asthma

T Cell, Ig Domain, Mucin Domain-2 Gene-Deficient Mice Reveal a Novel Mechanism for the Regulation of Th2 Immune Responses and Airway Inflammation

Structure and Function of CLCA Proteins

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