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题目:: T cell-induced airway smooth muscle cell proliferation via the epidermal growth factor receptor.
作者:: Al Heialy(Saba),Risse(Paul-Andre),Zeroual(Melissa A),Roman(Horia N),Tsuchiya(Kimitake),Siddiqui(Sana),Laporte(Stephane A),Martin(James G)
状态:: 发布时间2013-10-02 , 更新时间 2016-11-25
期刊:: Am J Respir Cell Mol Biol
摘要:: 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.
语言:: eng
DOI:: 10.1165/rcmb.2012-0356OC

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