Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3/8 complex.

Celastrol, a bioactive molecule extracted from the plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and COMMD8 (COMMD3/8 complex), a signaling adaptor for chemoattractant receptors.

Control of immune cell trafficking through inter-organ communication.

Cell migration is a cardinal feature of the immune system. Immune cell trafficking is orchestrated principally by chemokines and adhesion molecules, which guide the cells to the right place and at the right time to efficiently induce immune responses. Recent studies have demonstrated that signals from other organ systems influence the expression of and responsiveness to these guidance cues and consequentially immune cell migration.

The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors.

Lymphocyte migration is mediated by G protein-coupled receptors (GPCRs) that respond to chemoattractive molecules. After their activation, GPCRs are phosphorylated by different GPCR kinases (GRKs), which produces distinct functional outcomes through β-arrestins. However, the molecular machinery that targets individual GRKs to activated GPCRs remains elusive.

Adrenergic control of lymphocyte trafficking and adaptive immune responses.

Since the beginning of the last century, substantial evidence has suggested that various aspects of the immune system are influenced by the activity of the nervous system. However, the cellular and molecular basis for the neural control of immune responses has emerged only in the past decade. Recent studies have shown that adrenergic nerves control trafficking of immune cells through cell-type-specific mechanisms.

Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes.

Various aspects of the immune system display circadian rhythms. Although lymphocyte trafficking has been suggested to show diurnal variations, the mechanisms and influences on immune responses are unclear. Here, we show in mice that inputs from adrenergic nerves contribute to the diurnal variation of lymphocyte recirculation through lymph nodes (LNs), which is reflected in the magnitude of the adaptive immune response.

Rituximab therapy for Epstein-Barr virus-related chronic hepatitis following living donor kidney transplantation.

A patient who underwent living donor kidney transplantation was infected with Epstein-Barr virus (EBV) that resulted in persistent EBV infection and EBV-associated chronic hepatitis, determined by abnormally elevated anti-EBV antibody titers and high frequency of EBV-infected B lymphocytes. Despite decreases in immunosuppressant doses, persistent EBV infection and chronic hepatitis persisted for several years. Therapy using anti-CD20 monoclonal antibody (rituximab) virtually eliminated peripheral B lymphocytes and EBV-encoded small RNA 1 (EBER-1)-positive cells.

Glomerular proteinuria induces heme oxygenase-1 gene expression within renal epithelial cells.

To clarify the patterns of heme oxygenase-1 (HO-1) production within the human kidney, we examined HO-1 mRNA expression in various renal diseases and compared the patterns with those of HO-1 protein expression and these data with the clinical features. The degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta(2)-microglobulin (beta(2)-mg), and creatinine were determined. In situ hybridization and immunohistochemical studies were performed to evaluate HO-1 expression.

Selective protection of renal tubular epithelial cells by heme oxygenase (HO)-1 during stress-induced injury.

Background: The renal pathology of human heme oxygenase (HO)-1 deficiency is characterized by advanced tubulointerstitial injury, whereas the glomerular structures are affected little. These facts suggest that the renal tubuli are dependent on intrinsic HO-1 production for their survival under oxidative stresses.

Methods: We compared the patterns of HO-1 expression by primary cultured human mesangial cells (HMCs) and renal proximal tubular epithelial cells (HRPTECs) in vitro.