T Cell-Induced Airway Smooth Muscle Cell Proliferation via the Epidermal Growth Factor Receptor.

American journal of respiratory cell and molecular biology

PubMedID: 23656597

Al Heialy S, Risse PA, Zeroual MA, Roman HN, Tsuchiya K, Siddiqui S, Laporte SA, Martin JG. T Cell-Induced Airway Smooth Muscle Cell Proliferation via the Epidermal Growth Factor Receptor. Am J Respir Cell Mol Biol. 2013;.
Allergic asthma is a heterogeneous disease with no curative therapies. T cells infiltrate the airway smooth muscle (ASM) layer and may be implicated in airway remodeling and the increase of ASM mass, a cardinal feature of asthma. The mechanism by which CD4+ T cells drive airway remodeling remains unknown. The objective of this study was to determine the T cell-mediated mechanism of ASM cell proliferation. We hypothesized that CD4+ T cells adhere to ASM cells via CD44 and induce ASM cell proliferation through the activation of the epidermal growth factor receptor (EGFR). A co-culture model showed that contact of antigen-stimulated CD4+ T cells with ASM cells induces high levels of EGFR ligand expression in CD4+ T cells and activation of matrix metalloprotease (MMP)-9, required for the shedding of EGFR ligands. Inhibition of EGFR and MMP-9 prevented the increase of ASM cell proliferation following co-culture. The hyaluronan receptor CD44 is the dominant mediator of tight adherence of T cells to ASM, is colocalized with MMP-9 on the cell surface and neutralization of CD44 prevents ASM cell hyperplasia. These data provide a novel mechanism by which antigen-stimulated CD4+ T cells induce remodeling indicative of a direct trophic role for CD4+ T cells.