title: T cell-induced airway smooth muscle cell proliferation via the epidermal growth factor receptor.
abstract: 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. This study sought 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 coculture model showed that the contact of antigen-stimulated CD4(+) T cells with ASM cells induced high levels of EGFR ligand expression in CD4(+) T cells and the activation of matrix metalloproteinase (MMP)-9, required for the shedding of EGFR ligands. The inhibition of EGFR and MMP-9 prevented the increase of ASM cell proliferation after coculture. The hyaluronan receptor CD44 is the dominant mediator of the tight adherence of T cells to ASM and is colocalized with MMP-9 on the cell surface. Moreover, the neutralization of CD44 prevents ASM cell hyperplasia. These data provide a novel mechanism by which antigen-stimulated CD4(+) T cells induce the remodeling indicative of a direct trophic role for CD4(+) T cells.
authors: 1 Meakins Christie Laboratories, and.
authors: Saba
authors: S
authors: Al Heialy
authors: Paul-Andre
authors: PA
authors: Risse
authors: Melissa A
authors: MA
authors: Zeroual
authors: Horia N
authors: HN
authors: Roman
authors: Kimitake
authors: K
authors: Tsuchiya
authors: Sana
authors: S
authors: Siddiqui
authors: Stephane A
authors: SA
authors: Laporte
authors: James G
authors: JG
authors: Martin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000276:immunology; D008213:Lymphocyte Activation; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018960:Hyaluronan Receptors; C483803:Egfr protein, rat; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9