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Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-TH2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4+ T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop TH2 cells. These findings suggest that TH2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.

The experiment aimed to investigate the protective effects of Lycium barbarum polysaccharides (LBP) on aspirin (ASA) -induced intestinal injury in mice. The twenty-four 7-week-old male Kunming mice were randomly divided into a control group, aspirin model group (ASA group), and Lycium barbarum polysaccharide group (LBP group) after seven days of adaptive feeding, with eight mice in each group. The experimental period was 12 days. In the first six days of the experiment, the control group was gavage 200 mg/kg normal saline, and the ASA group and the LBP group were gavage the same amount of aspirin. On the last six days of the experiment, the LBP group was gavage 75 mg/kg LBP, and the control group and ASA group were gavage the same amount of normal saline. The results showed that compared with the control group, the jejunal villus height (VH) of the ASA group was significantly decreased (P<0.05) and villus height/crypt depth (VH/CD) was extremely decreased (P<0.01), the activity of superoxide dismutase (SOD) in the ileum was extremely decreased (P<0.01), the content of malondialdehyde (MDA) in the jejunum and ileum was extremely increased (P<0.01). Compared with the ASA group, the LBP group significantly decreased kidney index (P<0.05), extremely increased VH/CD in jejunum and SOD activity in jejunum and ileum (P<0.01), and extremely decreased MDA content in jejunum and ileum (P<0.01). The study indicates that LBP can enhance the antioxidant capacity of jejunum and ileum in ASA-induced intestinal injury in mice, improve intestinal morphology, and alleviate intestinal injury in mice. [ABSTRACT FROM AUTHOR]

Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-TH2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4+ T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop TH2 cells. These findings suggest that TH2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling. [ABSTRACT FROM AUTHOR]