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Gab2 和 Gab3 通过调节巨噬细胞和 CD8 T 细胞的激活来冗余性地抑制结肠炎。

Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8 T-Cell Activation.

机构信息

Division of Hem/Onc/BMT, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, United States.

BloodCenter of Wisconsin, Milwaukee, WI, United States.

出版信息

Front Immunol. 2019 Mar 18;10:486. doi: 10.3389/fimmu.2019.00486. eCollection 2019.

DOI:10.3389/fimmu.2019.00486
PMID:30936879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6431666/
Abstract

Inflammatory Bowel Disease (IBD) is a multi-factorial chronic inflammation of the gastrointestinal tract prognostically linked to CD8 T-cells, but little is known about their mechanism of activation during initiation of colitis. Here, Grb2-associated binding 2/3 adaptor protein double knockout mice (Gab2/3) were generated. Gab2/3 mice, but not single knockout mice, developed spontaneous colitis. To analyze the cellular mechanism, reciprocal bone marrow (BM) transplantation demonstrated a Gab2/3 hematopoietic disease-initiating process. Adoptive transfer showed individual roles for macrophages and T-cells in promoting colitis development . In spontaneous disease, intestinal intraepithelial CD8 but much fewer CD4, T-cells from Gab2/3 mice with rectal prolapse were more proliferative. To analyze the molecular mechanism, reduced PI3-kinase/Akt/mTORC1 was observed in macrophages and T-cells, with interleukin (IL)-2 stimulated T-cells showing increased pSTAT5. These results illustrate the importance of Gab2/3 collectively in signaling responses required to control macrophage and CD8 T-cell activation and suppress chronic colitis.

摘要

炎症性肠病（IBD）是一种多因素的胃肠道慢性炎症，与 CD8 T 细胞密切相关，但对其在结肠炎起始时的激活机制知之甚少。本研究构建了 Grb2 相关结合蛋白 2/3 衔接蛋白双重敲除（Gab2/3）小鼠。Gab2/3 小鼠而非单敲除小鼠自发发生结肠炎。为分析细胞机制，进行了相互骨髓（BM）移植实验，结果表明 Gab2/3 具有造血疾病起始作用。过继转移实验显示巨噬细胞和 T 细胞在促进结肠炎发展中各自发挥作用。在自发性疾病中，直肠脱垂的 Gab2/3 小鼠肠道上皮内 CD8 T 细胞而非 CD4 T 细胞增殖更多。为分析分子机制，观察到巨噬细胞和 T 细胞中 PI3-激酶/Akt/mTORC1 减少，IL-2 刺激的 T 细胞中 pSTAT5 增加。这些结果表明 Gab2/3 在控制巨噬细胞和 CD8 T 细胞激活以及抑制慢性结肠炎所需的信号转导反应中具有重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/4b4b17792c01/fimmu-10-00486-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/ddab7470382d/fimmu-10-00486-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/4b4b17792c01/fimmu-10-00486-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/02003cb4ca99/fimmu-10-00486-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/58004726040a/fimmu-10-00486-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/a4e37bae8447/fimmu-10-00486-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/834ca22fd5af/fimmu-10-00486-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/368cdb46460e/fimmu-10-00486-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/d7ccad48645d/fimmu-10-00486-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/ddab7470382d/fimmu-10-00486-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3b/6431666/4b4b17792c01/fimmu-10-00486-g0008.jpg

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2
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Arthritis Res Ther. 2018 Jul 20;20(1):149. doi: 10.1186/s13075-018-1639-3.
3
: Does Gastritis Prevent Colitis?
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JCI Insight. 2023 Mar 22;8(6):e162701. doi: 10.1172/jci.insight.162701.
4
Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.青子止痛汤治疗溃疡性结肠炎分子机制的网络药理学及分子对接分析
Front Pharmacol. 2022 Feb 8;13:727608. doi: 10.3389/fphar.2022.727608. eCollection 2022.
5
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6
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