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βig-h3 结构胶原蛋白改变胰腺癌中巨噬细胞的表型和功能。

βig-h3-structured collagen alters macrophage phenotype and function in pancreatic cancer.

作者信息

Bachy Sophie, Wu Zhichong, Gamradt Pia, Thierry Kevin, Milani Pascale, Chlasta Julien, Hennino Ana

机构信息

Cancer Research Center of Lyon, UMR INSERM1052, CNRS5286, 69373 Lyon, France.

Université Lyon 1, 69000 Lyon, France.

出版信息

iScience. 2022 Jan 10;25(2):103758. doi: 10.1016/j.isci.2022.103758. eCollection 2022 Feb 18.

DOI:10.1016/j.isci.2022.103758
PMID:35146384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8816720/
Abstract

Macrophages play an important role in immune and matrix regulation during pancreatic adenocarcinoma (PDAC). Collagen deposition massively contributes to the physical and functional changes of the tissue during pathogenesis. We investigated the impact of thick collagen fibers on the phenotype and function of macrophages. We recently demonstrated that the extracellular protein βig-h3/TGFβi (Transforming growth factor-β-induced protein) plays an important role in modulating the stiffness of the pancreatic stroma. By using atomic force microscopy, we show that βig-h3 binds to type I collagen and establishes thicker fibers. Macrophages cultured on βig-h3-structured collagen layers display a different morphology and a pro-tumoral M2 phenotype and function compared to those cultured on non-structured collagen layers. injection of those instructed CD206CD163 macrophages was able to suppress T cell responses. These results reveal for the first time that the collagen structure impacts the phenotype and function of macrophages by potentiating their immunosuppressive features.

摘要

巨噬细胞在胰腺腺癌（PDAC）的免疫和基质调节中发挥重要作用。胶原蛋白沉积在发病过程中对组织的物理和功能变化有很大影响。我们研究了粗大胶原纤维对巨噬细胞表型和功能的影响。我们最近证明，细胞外蛋白βig-h3/TGFβi（转化生长因子-β诱导蛋白）在调节胰腺基质硬度方面发挥重要作用。通过原子力显微镜，我们发现βig-h3与I型胶原结合并形成更粗大的纤维。与在非结构化胶原层上培养的巨噬细胞相比，在βig-h3结构化胶原层上培养的巨噬细胞表现出不同的形态以及促肿瘤的M2表型和功能。注射这些被诱导的CD206CD163巨噬细胞能够抑制T细胞反应。这些结果首次揭示，胶原结构通过增强巨噬细胞的免疫抑制特性来影响其表型和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/328c09b52a7b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/a64518d8ef9b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/2dbdf6d8e602/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/52837f427a64/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/a8ad9fc47522/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/f14c26217d70/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/1103a721d217/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/f4d498840cea/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/328c09b52a7b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/a64518d8ef9b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/2dbdf6d8e602/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/52837f427a64/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/a8ad9fc47522/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/f14c26217d70/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/1103a721d217/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/f4d498840cea/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6e/8816720/328c09b52a7b/gr7.jpg

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Nat Immunol. 2020 Apr;21(4):442-454. doi: 10.1038/s41590-020-0620-x. Epub 2020 Mar 9.
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