Matrix Metalloproteinase-2 Conditions Human Dendritic Cells to Prime Inflammatory TH2 Cells via an IL-12- and OX40L-Dependent Pathway

Emmanuelle Godefroy, Olivier Manches, Brigitte Dréno, Tsivia Hochman, Linda Rolnitzky, Nathalie Labarrière, Yannick Guilloux, Judith Goldberg, Francine Jotereau, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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 TH2 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 TH2 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.

Original languageEnglish
Pages (from-to)333-346
Number of pages14
JournalCancer Cell
Volume19
Issue number3
DOIs
StatePublished - 8 Mar 2011
Externally publishedYes

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