IL-26 modulates T cell function in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is an aberrant autoimmune condition mediated by T cell abnormality, which may cause fulminant liver failure and persistent liver injury. This study aimed to disclose the histopathological and functional engagement of interleukin (IL)-26, a potent inflammation mediator, in AIH disease progression. METHODS: We conducted immunohistochemical staining on liver biopsy samples to evaluate intrahepatic expression of IL-26. Cellular sources of hepatic IL-26 were detected by confocal microscopy. Flow cytometry was employed to determine the immunological alterations of CD4+ and CD8+ T cells following in vitro IL-26 treatment on primary peripheral blood mononuclear cells from healthy controls. RESULTS: Statistically significant increase in IL-26 level was observed in AIH (n = 48) liver samples in comparison with patients having chronic hepatitis B (n = 25), nonalcoholic fatty liver disease (n = 18), and healthy donors for living donor liver transplantation (n = 10). The number of intrahepatic IL-26+ cells was positively correlated with histological and serological severity. An immunofluorescence staining indicated that liver-infiltrating CD4+ T cells, CD8+ T cells, and CD68+ macrophages orchestrated IL-26 secretion in AIH. Both CD4+ and CD8+ T cells demonstrated effective activation, lytic, and proinflammatory functions upon IL-26 stimulation. CONCLUSION: We observed elevated IL-26 in AIH liver which promoted T cell activation and cytotoxic capacity, indicating a therapeutic potential of IL-26 intervention in AIH.

CD8+ T cells actively penetrate hepatocytes via the CD44/p-ERM/F-actin pathway in autoimmune hepatitis.

OBJECTIVE: Emperipolesis is a pathological feature for the diagnosis of autoimmune hepatitis (AIH). We have previously found that CD8+ T cells participated in the emperipolesis in AIH. In this study we aimed to clarify the characteristics and molecular mechanisms of emperipolesis in patients with AIH in vitro and in mice with α-Galactosylceramide (α-GalCer)-induced acute hepatitis. METHODS: The peripheral blood mononuclear cells (PBMC) of patients with various chronic liver diseases and healthy controls were co-cultured with hepatic cell lines to induce emperipolesis in vitro. Confocal staining was performed to illustrate the cellular types and potential mechanisms of emperipolesis in AIH. In addition, a murine model of α-GalCer-induced acute hepatitis that mimics human AIH was used to confirm the role of CD44/p-ERM/F-actin in the emperipolesis process in vivo. RESULTS: In the co-cultured system of PBMC and hepatic cell line, emperipolesis was observed most commonly in patients with AIH. The main cells participating in emperipolesis were CD8+ T cells, and they penetrated hepatic cells actively via the CD44/p-ERM/F-actin pathway. As a result, most CD8+ T cells engulfed by hepatic cells underwent apoptosis. In the α-GalCer-induced acute hepatitis model, emperipolesis was observed around the inflammatory foci and was inhibited by the ezrin phosphorylation inhibitor NSC668394. Similarly, activated murine CD8+ T cells penetrated primary hepatocytes via the CD44/p-ERM/F-actin pathway in vitro. CONCLUSIONS: CD8+ T cells penetrate hepatic cells actively via the CD44/p-ERM/F-actin signaling pathway and undergo apoptosis. This may be a compensatory mechanism to attenuate the overwhelming immune attack in AIH.

[Carbon and nitrogen stable isotopes technology in the researches on alpine meadow ecosystem in Qinghai-Tibet Plateau: Progress and prospect]. / ç¢³æ°®ç¨³å®šåŒä½ç´ æŠ€æœ¯åœ¨é’è—é«˜åŽŸé«˜å¯’è‰ç”¸ç”Ÿæ€ç³»ç»Ÿç ”ç©¶ä¸­çš„åº”ç”¨: 进展与展望.

Carbon and nitrogen stable isotopic technique has been widely used in research of glassland ecosystems. Here, we summarized studies using carbon and nitrogen stable isotopes in the alpine meadow ecosystem on the Qinghai-Tibet Plateau. Firstly, we reviewed the environmental factors which influenced carbon and nitrogen isotope composition (δ13C and δ15N) of plants and soils in alpine meadow, such as altitude, moisture, fertilization, grassland degradation, and temperature. The values of plant δ13C were positively correlated with altitude, and negatively correlated with atmospheric pressure, grassland degradation and temperature. The relationship between plant δ13C and precipitation was non-linear. The values of soil δ13C were positively correlated with altitude and grassland degradation. The values of plant δ15N were positively correlated with soil moisture and fertilization, and negatively correlated with grassland degradation. Secondly, we reviewed the current application and progresses of 13C and 15N in the identification of plant photosynthetic type, water use, nutrient transport along food chain and carbon and nitrogen cycle in the alpine meadow. Finally, we prospected the 13C and 15N isotopes application in researches on soil organic carbon and soil respiration in the alpine meadow, transitions of vegetation type, and climate change, soil N2O trace, exploration of vegetation degradation, identification of the origin of Tibetan medicine and animal food, etc. 13C and 15N isotopes could be widely used and play important roles in researches on the alpine ecosystems.

[Changes of soil enzyme activities and nutrients across different succession stages of grazing alpine Kobresia grassland.] / æ”¾ç‰§é«˜å¯’åµ©è‰è‰åœ°ä¸åŒæ¼”æ›¿é˜¶æ®µåœŸå£¤é ¶æ´»æ€§åŠå »åˆ†æ¼”å˜ç‰¹å¾.

The variation of soil enzyme activity and relevance with soil nutrients was examined in multistable grazing alpine Kobresia grassland, including Gramineae-Kobresia humilis community, K. humilis community, K. pygmaea community at thickened stage, K. pygmaea community at cracked stage and forb-black soil type secondary bare land. The results showed that the vegetation coverage and aboveground biomass successively decreased with degenerative succession. The belowground biomass was the highest in the K. pygmaea community at thickened and cracked stages. The activities of soil sucrase, urease, cellulase, alkaline phosphatase and aryl sulfatase were higher at the surface soil layer (0-10 cm) than those at the subsurface soil layer (10-20 cm), while the pattern of chitinase activity was contrary. The activities of cellulase, alkaline phosphatase and aryl sulfatase were the highest in the Gramineae-K. humilis community and the lowest at the forb-black soil type secondary bare land, and they slightly increased during the thickened stage of K. pygmaea community. Chitinase activity was relatively high at the middle three stages, while urease and sucrase activity had an obvious increase in the forb-black soil type secondary bare land. Soil moisture, ammonium, alkali-hydrolyzable nitrogen, total nitrogen, total carbon and organic carbon successively decreased with degenerative succession, whereas the concentrations of nitrate and available phosphorus increased at the latter two succession stages. The activities of the other enzymes, except for chitinase, were significantly positively correlated with the soil available phosphorus, ammonium, alkali-hydrolyzed nitrogen, total carbon, and organic carbon, and negatively correlated with soil pH. The activities of cellulose, alkaline phosphatase and aryl sulfatase were significantly positively correlated with soil moisture and total nitrogen. The main factors affecting soil enzyme activity were available phosphorus and ammonium. Soil enzymes showed different evolutionary trends influenced by grazing degradation succession in the alpine grassland, with a synergistic effect with soil nut-rients. Moreover, severely degraded extreme environments may stimulate soil enzyme activities related to nitrogen and carbon transformation.

Nutrient-induced shifts of dominant species reduce ecosystem stability via increases in species synchrony and population variability.

The mechanisms underlying nutrient-induced diversity-stability relationships have been examined extensively. However, the effects of nutrient-induced shifts of dominant species on ecosystem stability have rarely been evaluated. We compiled a dataset from a long-term nitrogen (N) and phosphorus (P) enrichment experiment conducted in an alpine grassland on the Tibetan Plateau to test the effects of nutrient-induced shifts of dominant species on stability. Our results show that N enrichment increased synchrony among the dominant species, which contributed to a significant increase in synchrony of the whole community. Meanwhile, N-induced shifts in dominant species composition significantly increased population variability. Increases in species synchrony and population variability resulted in a decline in ecosystem stability. Our study has important implications for progress in understanding the role of plant functional compensation in the stability of ecosystem functions, which is critical for better understanding the mechanisms driving both community assembly and ecosystem functions.

CTHRC1 expression in primary biliary cholangitis.

OBJECTIVES: Collagen triple helix repeat containing-1 (CTHRC1) is a highly conserved extracellular matrix glycoprotein that is overexpressed in two murine models of cholestatic liver fibrosis. Elevated CTHRC1 has been found to attenuate liver fibrosis in these murine models, thus we aimed to study the expression of CTHRC1 in patients with cholestatic liver diseases and its correlation with hepatic conditions. METHODS: Ninety patients with chronic liver disease, including 48 had primary biliary cholangitis (PBC), 18 had primary sclerosing cholangitis (PSC) and 24 had chronic hepatitis B (CHB), together with five healthy controls (HC), were recruited to this study. Participants' liver sections were analyzed using immunohistochemistry. Serum CTHRC1 levels in another cohort of 59 patients with PBC and 10 age-matched HC were detected by enzyme-linked immunosorbent assay. RESULTS: CTHRC1 protein was primarily expressed in activated hepatic stellate cells (HSC). CTHRC1 expression was significantly increased in the PBC and PSC groups, compared with the HC and CHB groups. Importantly, the hepatic fibrosis stage of the PBC group was positively correlated with hepatic CTHRC1 expression (r = 0.425, P = 0.003). Meanwhile, there were significant correlations between serum CTHRC1 levels and both the degrees of hepatic inflammation and fibrosis stage in the PBC group (r = 0.300, P = 0.022; r = 0.321, P = 0.012). CONCLUSION: CTHRC1 may play a role in hepatic fibrogenesis in PBC and that serum CTHRC1 may be a potential novel noninvasive biomarker in the assessment of liver fibrosis and inflammation.

[Periodic fluctuation features of air temperature, precipitation, and aboveground net primary production of alpine meadow ecosystem on Qinghai-Tibetan Plateau].

With Mexican Hat function as mother function, a wavelet analysis was conducted on the periodic fluctuation features of air temperature, precipitation, and aboveground net primary production (ANPP) in the Alpine Meadow Ecosystem Research Station, Chinese Academy of Sciences from 1980 to 2007. The results showed that there was a main period of 13 years for the annual fluctuations of air temperature, precipitation, and ANPP. A secondary period of 2 years for the annual fluctuations of air temperature and ANPP had lesser influence, whereas that of 4 years for the annual fluctuation of precipitation had greater effect. Lagged correlation analysis indicated that the annual fluctuation of ANNP was mainly controlled by the air temperature in a 20 years scale and had a weak 5-9 years lag effect, but there was a less correlation between ANPP and precipitation.