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Matrix metalloproteinase-2 Conditions Human Dendritic Cells to Prime Inflammatory T(H)2 Cells via an IL-12- And OX40L-dependent Pathway

Abstract : Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme degrading the extracellular matrix and overexpressed by many tumors. Here, we documented the presence of MMP-2-specific CD4(+) T cells in tumor-infiltrating lymphocytes (TILs) from melanoma patients. Strikingly, MMP-2-specific CD4(+) T cells displayed an inflammatory T(H)2 profile, i.e., mainly secreting TNF-α, IL-4, and IL-13 and expressing GATA-3. Furthermore, MMP-2-conditioned dendritic cells (DCs) primed naïve CD4(+) T cells to differentiate into an inflammatory T(H)2 phenotype through OX40L expression and inhibition of IL-12p70 production. MMP-2 degrades the type I IFN receptor, thereby preventing STAT1 phosphorylation, which is necessary for IL-12p35 production. Active MMP-2, therefore, acts as an endogenous type 2 "conditioner" and may play a role in the observed prevalence of detrimental type 2 responses in melanoma.
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Submitted on : Tuesday, February 18, 2020 - 6:35:45 PM
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Emmanuelle Godefroy, Olivier Manches, Brigitte Dréno, Tsivia Hochman, Linda Rolnitzky, et al.. Matrix metalloproteinase-2 Conditions Human Dendritic Cells to Prime Inflammatory T(H)2 Cells via an IL-12- And OX40L-dependent Pathway. Cancer Cell, Elsevier, 2011, 19 (3), pp.333-346. ⟨10.1016/j.ccr.2011.01.037⟩. ⟨inserm-02483749⟩

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