基质金属蛋白酶-2 通过一种依赖于白细胞介素-12 和 OX40L 的途径调节树突状细胞，从而诱导炎症性 T(H)2 细胞的产生。
Matrix metalloproteinase-2 conditions human dendritic cells to prime inflammatory T(H)2 cells via an IL-12- and OX40L-dependent pathway.
机构信息
New York University Langone Medical Center, Cancer Institute, New York, NY, USA.
出版信息
Cancer Cell. 2011 Mar 8;19(3):333-46. doi: 10.1016/j.ccr.2011.01.037.
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.
摘要
基质金属蛋白酶-2（MMP-2）是一种蛋白水解酶，可降解细胞外基质，许多肿瘤均过度表达 MMP-2。在此，我们在黑色素瘤患者肿瘤浸润淋巴细胞（TIL）中记录到 MMP-2 特异性 CD4+T 细胞的存在。值得注意的是，MMP-2 特异性 CD4+T 细胞表现出炎症性 T(H)2 表型，即主要分泌 TNF-α、IL-4 和 IL-13，并表达 GATA-3。此外，MMP-2 条件化树突状细胞（DC）通过 OX40L 表达和抑制 IL-12p70 产生，将幼稚 CD4+T 细胞初始化为炎症性 T(H)2 表型。MMP-2 降解 I 型 IFN 受体，从而阻止 STAT1 磷酸化，而 STAT1 磷酸化是 IL-12p35 产生所必需的。因此，活性 MMP-2 作为内源性 2 型“调节剂”，可能在黑色素瘤中观察到的有害 2 型反应的流行中发挥作用。
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