Uncontrolled natural killer (NK) cell activation during the early response to acute viral infection can lead to severe immunopathology, and the mechanisms NK cells use to achieve self‐tolerance in such contexts are currently unclear. Here, NK cells up‐regulated a coinhibitory receptor, T‐cell Ig and ITIM domain (TIGIT), during challenge with the viral double‐stranded RNA (dsRNA) analog poly I:C. Blocking TIGIT by antibody treatment in vivo or a genetic deficiency in Tigit enhanced NK cell activation and aggravated liver injury in a poly I:C/D‐GalN‐induced model of acute fulminant hepatitis, suggesting that TIGIT is normally required for protecting against NK cell‐mediated liver injury. Furthermore, adoptively transferring Tigit−/− NK cells into NK cell‐deficient Nfil3−/− mice also resulted in elevated liver injury. Reconstituting Kupffer cell‐depleted mice with poliovirus receptor (PVR/CD155, a TIGIT ligand)‐silenced Kupffer cells led to aggravated liver injury in a TIGIT‐dependent manner. Blocking TIGIT in an NK‐Kupffer cell coculture in vitro enhanced NK cell activation and interferon‐gamma (IFN‐γ) production in a PVR‐dependent manner. We also found that TIGIT was up‐regulated selectively on NK cells and protected against liver injury in an acute adenovirus infection model in both an NK cell‐ and Kupffer cell‐dependent manner. Knocking down PVR in Kupffer cells resulted in aggravated liver injury in response to adenovirus infection in a TIGIT‐dependent manner. Conclusion: TIGIT negatively regulates NK‐Kupffer cell crosstalk and alleviates liver injury in response to poly I:C/D‐GalN challenge or acute adenovirus infection, suggesting a novel mechanism of NK cell self‐tolerance in liver homeostasis during acute viral infection. (Hepatology 2014;59:1715–1725)

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To explore the clinicopathological characteristics and outcomes of light chain deposition disease (LCDD) in a Chinese population, we retrospectively studied the clinicopathological data, treatment, and outcomes of 48 patients with biopsy-proven LCDD from a single center. Among the patients, there were 29 males and 19 females, with an average age of 51 years. The patients presented with hypertension (79.2 %), edema (60.4 %), renal insufficiency (95.8 %), anemia (93.8 %), nephrotic proteinuria (≥3.0 g/24 h) (44.4 %), and hematuria (75.0 %). Moreover, 33.3 % had hypocomplementemia of C3, and 25 % were diagnosed with multiple myeloma. Serum immunofixation electrophoresis and a serum free light chain assay showed that 26.7 and 85.4 % of patients presented with monoclonal immunoglobulin, respectively. Nodular mesangial sclerosis was identified in 83.3 % of our cases and vascular involvement was observed in 77.1 % by light microscopy. Over an average of 22 months of follow-up, the mean renal survival was 32.5 months. Of the patients, 34.1 % had stable or improved renal dysfunction, 2.3 % had worsening renal function, and 63.6 % progressed to end-stage renal disease. Of the 33 patients receiving chemotherapy, 15 patients had stable or improved renal function and the renal survival was higher in patients with hematological and renal responses than in those without. The independent predictors of ESRD by multivariate analysis were serum creatinine (p = 0.008) and urinary retinol binding protein (RBP) (p = 0.045). In conclusion, LCDD was characterized in Chinese patients by renal dysfunction, hypertension, anemia, proteinuria, abnormal free light chain ratios, and less overt hematologic malignancies. Serum creatinine and RBP were independent prognostic factors of LCDD. As better hematologic and renal responses to chemotherapy were associated with improved renal survival, there is an urgent need for multicenter and prospective studies to establish the standardized therapy for LCDD.

Background: Breast cancer is a major malignancy affecting females worldwide. It is the most common cause of death from cancer in women. Cell lines are widely used in laboratory research and particularly as in vitro models in cancer research. But we found that the routinely used breast cancer cell lines were mostly derived from Caucasians or African-Americans. There were few standard models to study the pathogenic mechanism at molecular level and cell signaling pathway of breast cancer for Asian patients. It is quite necessary to establish new breast cancer cell lines from xanthoderm to study the pathogenic mechanism and therapeutic methods.