Macrophages and β-cells are responsible for CXCR2-mediated neutrophil infiltration of the pancreas during autoimmune diabetes.
Macrophages and β-cells are responsible for CXCR2-mediated neutrophil infiltration of the pancreas during autoimmune diabetes.
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DOI：
10.15252/emmm.201404144
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发表时间：
2014-08
影响因子：
11.1
通讯作者：
Lehuen A
中科院分区：
文献类型：
--
作者：
Diana J;Lehuen A
自身免疫性1型糖尿病（T1 D）的发展是由胰腺β细胞与先天性和适应性免疫系统之间的相互作用引起的，最终通过自身反应性T细胞破坏胰岛素分泌β细胞。这种致糖尿病的过程在出生后的第一周开始，通过先天免疫细胞，特别是中性粒细胞浸润胰岛。在这里，我们的目的是确定细胞和分子机制，导致募集中性粒细胞在非肥胖糖尿病（NOD）小鼠的胰岛。在这里，我们表明胰岛中的中性粒细胞募集是由炎性巨噬细胞和β细胞本身控制的。巨噬细胞和β细胞产生趋化因子CXCL 1和CXCL 2，将表达CXCR 2的中性粒细胞从血液募集到胰岛。我们进一步表明，胰腺巨噬细胞分泌IL-1β诱导β细胞产生CXCR 2配体。最后，使用CXCR 2拮抗剂在早期阻断中性粒细胞募集抑制了致糖尿病性T细胞应答和自身免疫性糖尿病的后期发展，支持了这种方法的治疗潜力。免疫学;代谢学
Autoimmune type 1 diabetes (T1D) development results from the interaction between pancreatic β-cells, and the innate and the adaptive immune systems culminating with the destruction of the insulin-secreting β-cells by autoreactive T cells. This diabetogenic course starts during the first postnatal weeks by the infiltration of the pancreatic islets by innate immune cells and particularly neutrophils. Here, we aim to determine the cellular and molecular mechanism leading to the recruitment of this neutrophils in the pancreatic islets of non-obese diabetic (NOD) mice. Here, we show that neutrophil recruitment in the pancreatic islets is controlled by inflammatory macrophages and β-cells themselves. Macrophages and β-cells produce the chemokines CXCL1 and CXCL2, recruiting CXCR2-expressing neutrophils from the blood to the pancreatic islets. We further show that pancreatic macrophages secrete IL-1β-inducing CXCR2 ligand production by the β-cells. Finally, the blockade of neutrophil recruitment at early ages using CXCR2 antagonist dampens the diabetogenic T-cell response and the later development of autoimmune diabetes, supporting the therapeutic potential of this approach. Subject Categories Immunology; Metabolism
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中性粒细胞在免疫，炎症及以后的各种新型功能。
DOI：
10.1084/jem.20122220
发表时间：
2013-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mócsai A
通讯作者：
Mócsai A
影响因子：
7.7
作者：
Ablamunits V;Henegariu O;Hansen JB;Opare-Addo L;Preston-Hurlburt P;Santamaria P;Mandrup-Poulsen T;Herold KC
通讯作者：
Herold KC
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
15.9
作者：
Citro, Antonio;Cantarelli, Elisa;Piemonti, Lorenzo
通讯作者：
Piemonti, Lorenzo