Prominent B-Cell Signature Differentiates Discoid from Subacute Cutaneous Lupus Erythematosus.

Although B cells account for a significant proportion of the lymphocytic infiltrate in discoid lupus erythematosus (DLE), their contribution to pathogenesis is unknown. In this study, we compare the immune landscape of 17 subjects with DLE with that of 21 subjects with subacute cutaneous lupus erythematosus using transcriptomic and histologic analyses of lesional skin. A few of the subjects (3 of 17 subjects with DLE, and 5 of 21 subjects with subacute cutaneous lupus erythematosus) had concomitant systemic lupus erythematosus.

Human cutaneous B cells: what do we really know?

B cells play many critical roles in the systemic immune response, including antibody secretion, antigen presentation, T cell co-stimulation, and pro- and anti-inflammatory cytokine production. However, the contribution of B cells to the local immune response in many non-lymphoid tissues, such as the skin, is incompletely understood. Cutaneous B cells are scarce except in certain malignant and inflammatory conditions, and as such, have been poorly characterized until recently.

Anti-TIF1gamma Antibody-Positive Dermatomyositis Associated with Myelodysplastic Syndrome: Response to Treatment.

Dermatomyositis (DM) classically presents as a dyad of typical cutaneous findings and varying degrees of proximal muscle weakness. Interestingly, the development of DM may signal underlying malignancy, and numerous myositis-specific autoantibodies have been associated with this paraneoplastic phenomenon. Positivity for anti-TIF1gamma antibody, in particular, raises suspicion for cancer-associated DM.

Epigenetic Suppression of SERPINB1 Promotes Inflammation-Mediated Prostate Cancer Progression.

Granulocytic myeloid infiltration and resultant enhanced neutrophil elastase (NE) activity is associated with poor outcomes in numerous malignancies. We recently showed that NE expression and activity from infiltrating myeloid cells was high in human prostate cancer xenografts and mouse -null prostate tumors. We further demonstrated that NE directly stimulated human prostate cancer cells to proliferate, migrate, and invade, and inhibition of NE attenuated xenograft growth.

Neutrophil elastase in the tumor microenvironment.

Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types.

Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase.

Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here, it is reported that granulocytic myeloid-derived suppressor cells (MDSC) are the predominant tumor-infiltrating cells in prostate cancer xenografts established in athymic nude mice.

Estrogen maintains myometrial tumors in a lymphangioleiomyomatosis model.

Lymphangioleiomyomatosis (LAM) is a rare disease in women. Patients with LAM develop metastatic smooth-muscle cell adenomas within the lungs, resulting in reduced pulmonary function. LAM cells contain mutations in tuberous sclerosis genes (TSC1 or TSC2), leading to up-regulation of mTORC1 activity and elevated proliferation.

Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo.

Objective: The regulation of vascular permeability, leukocyte trafficking, and the integrity of endothelial cell-cell contacts are closely linked by a complex mechanism of interregulation. Here, we investigate the role of Krev interaction-trapped 1 (KRIT1), an adherens junction accessory protein required for cell-cell junction stability, in regulating these vascular functions.

Methods And Results: Krit1(+/-) mice exhibited an enhanced edematous response to the complex inflammatory stimuli found in the passive K/BxN model of inflammatory arthritis and the murine air pouch model, yet leukocyte infiltration was unchanged.

Electroconvective instability in concentration polarization and nonequilibrium electro-osmotic slip.

This paper concerns the comparison of electroconvective instability in concentration polarization at an ion-selective membrane with previously reported nonequilibrium electro-osmotic instability. Electro-osmotic formulation represents an asymptotic limit case of the electroconvective one. An improved nonequilibrium electro-osmotic slip formula is derived.

Absence of bulk electroconvective instability in concentration polarization.

The problem of bulk electroconvective stability of quiescent electric conduction from an electrolyte solution into a charge-selective solid (ion-exchange membrane) has been revised. It is shown through a numerical solution of the linear stability problem that previously reported bulk electroconvective instability does not exist. This numerical result is supported by the short wave asymptotic analysis.