Expression of mucosa-related integrin αEβ7 on alveolar T cells in interstitial lung diseases

The expression of αEβ7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated αEβ7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), αE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of αE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed αE. Absolute alveolar CD8+αE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of αE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 ± 2.7%) and HP (70.0 ± 2.4%) compared with normals (30.0 ± 1.8%) (mean ± s.e.m.; P < 0.01). In sarcoidosis, the αE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 ± 1.5%), but increased proportions in stages II (50.0 ± 3.8%) and III (64.0 ± 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-β) bioactivity and αE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express αEβ7 and that distinct patterns of αEβ7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung

A role for atm in E-cadherin-mediated contact inhibition in epithelial cells

Ataxia telangiectasia is a hereditary pleiomorphic syndrome caused by loss of Atm, a phosphoprotein involved in multiple signaling pathways. Here, we propose a novel role for atm in cultured epithelial cells, namely the regulation of cell growth by contact inhibition. We show that atm is upregulated in epithelial cells reaching confluence. Conditional expression of the PI 3-Kinase domain of atm in non-confluent Tac-2 epithelial cells increases the expression of the anti-proliferative gene Tis-21 and downregulates key cell cycle regulator genes, such as cyclins A, B1, B2, E and E2. Finally, we demonstrate that upregulation of atm, and thus Tis-21, in confluent Tac-2 cells can be inhibited by an E-cadherin antibody blocking specifically homophilic E-cadherin interactions between adjacent cell surfaces. Altogether, these results suggest that atm could participate in a molecular pathway linking extracellular signalling to cell cycle control and may help further clarify the role of Atm in epithelial cell biology and carcinogenesis