MANF ameliorates DSS-induced mouse colitis via restricting Ly6C(hi)CX3CR1(int) macrophage transformation and suppressing CHOP-BATF2 signaling pathway.
MANF ameliorates DSS-induced mouse colitis via restricting Ly6C(hi)CX3CR1(int) macrophage transformation and suppressing CHOP-BATF2 signaling pathway.
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MANF通过限制Ly 6C（hi）CX 3CR 1（int）巨噬细胞转化和抑制CHOP-BATF 2信号通路改善DSS诱导的小鼠结肠炎。
DOI：
10.1038/s41401-022-01045-8
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发表时间：
2023-06
影响因子：
8.2
通讯作者：
Shen, Yu-xian
中科院分区：
文献类型：
--
作者：
Yang, Lin;Shen, Wen-wen;Shao, Wei;Zhao, Qing;Pang, Gao-zong;Yang, Yi;Tao, Xiao-fang;Zhang, Wei-ping;Mei, Qiong;Shen, Yu-xian
关键词：
Mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum stress-inducible secreting protein, has evolutionarily conserved immune-regulatory function that contributes to the negative regulation of inflammation in macrophages. In this study, we investigated the profiles of MANF in the macrophages of the patients with active inflammatory bowel disease (IBD) and the mice with experimental colitis, which was induced in both myeloid cell-specific MANF knockout mice and wild-type mice by 3% dextran sodium sulfate (DSS) for 7 days. We found that MANF expression was significantly increased in intestinal macrophages from both the mice with experimental colitis and patients with active IBD. DSS-induced colitis was exacerbated in myeloid cell-specific MANF knockout mice. Injection of recombinant human MANF (rhMANF, 10 mg·kg–1·d–1, i.v.) from D4 to D6 significantly ameliorated experimental colitis in DSS-treated mice. More importantly, MANF deficiency in myeloid cells resulted in a dramatic increase in the number of Ly6ChiCX3CRint proinflammatory macrophages in colon lamina propria of DSS-treated mice, and the proinflammatory cytokines and chemokines were upregulated as well. Meanwhile, we demonstrated that MANF attenuated Th17-mediated immunopathology by inhibiting BATF2-mediated innate immune response and downregulating CXCL9, CXCL10, CXCL11 and IL-12p40; MANF functioned as a negative regulator in inflammatory macrophages via inhibiting CHOP-BATF2 signaling pathway, thereby protecting against DSS-induced mouse colitis. These results suggest that MANF ameliorates colon injury by negatively regulating inflammatory macrophage transformation, which shed light on a potential therapeutic target for IBD.
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影响因子：
5
作者：
Glembotski CC
通讯作者：
Glembotski CC
DOI：
10.1155/2014/928461
发表时间：
2014
期刊：
ISRN inflammation
影响因子：
--
作者：
Gálvez J
通讯作者：
Gálvez J
影响因子：
16.6
作者：
Desalegn, Girmay;Pabst, Oliver
通讯作者：
Pabst, Oliver
影响因子：
9.1
作者：
Blaschitz, Christoph;Raffatellu, Manuela
通讯作者：
Raffatellu, Manuela
影响因子：
24.5
作者：
Cader, M. Zaeem;Kaser, Arthur
通讯作者：
Kaser, Arthur