Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23-induced psoriasis-like mouse model. We further showed that TGF-β and IL-23 enhance miR-210 expression by inducing HIF-1α, which recruits P300 and promotes histone H3 acetylation in the miR-210 promoter region. Our results reveal a crucial role for miR-210 in the immune imbalance of T lymphocyte subsets in psoriasis and suggest a potential therapeutic avenue.

Background Freshwater salinization may result in significant changes of microbial community composition and diversity, with implications for ecosystem processes and function. Earlier research has revealed the importance of large shifts in salinity on microbial physiology and ecology, whereas studies on the effects of smaller or narrower shifts in salinity on the microeukaryotic community in inland waters are scarce. Our aim was to unveil community assembly mechanisms and the stability of microeukaryotic plankton networks at low shifts in salinity. Results Here, we analyzed a high-resolution time series of plankton data from an urban reservoir in subtropical China over 13 consecutive months following one periodic salinity change ranging from 0 to 6.1‰. We found that (1) salinity increase altered the community composition and led to a significant decrease of plankton diversity, (2) salinity change influenced microeukaryotic plankton community assembly primarily by regulating the deterministic-stochastic balance, with deterministic processes becoming more important with increased salinity, and (3) core plankton subnetwork robustness was higher at low-salinity levels, while the satellite subnetworks had greater robustness at the medium-/high-salinity levels. Our results suggest that the influence of salinity, rather than successional time, is an important driving force for shaping microeukaryotic plankton community dynamics. Conclusions Our findings demonstrate that at low salinities, even small increases in salinity are sufficient to exert a selective pressure to reduce the microeukaryotic plankton diversity and alter community assembly mechanism and network stability. Our results provide new insights into plankton ecology of inland urban waters and the impacts of salinity change in the assembly of microbiotas and network architecture.

ObjectiveT cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations.MethodsPeripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases.ResultsSignificant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases.ConclusionsThese characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.