Generation of five induced pluripotent stem cell lines from patients with MECP2 Duplication Syndrome.

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.

Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans.

Tapinarof (GSK2894512) is a naturally derived topical treatment with demonstrated efficacy for patients with psoriasis and atopic dermatitis, although the biologic target and mechanism of action had been unknown. We demonstrate that the anti-inflammatory properties of tapinarof are mediated through activation of the aryl hydrocarbon receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue-human skin.

Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

Background: The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota.

Methods: Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics.

BAFF regulates follicular helper t cells and affects their accumulation and interferon-γ production in autoimmunity.

Objective: Follicular helper T (Tfh) cells are critical for the development of protective antibodies via germinal center (GC) B cell responses; however, uncontrolled Tfh cell expansion activates autoreactive B cells to produce antibodies that cause autoimmunity. The mechanisms that control Tfh cell homeostasis remain largely unknown. The aim of this study was to determine the contribution of BAFF to Tfh cell responses in autoimmunity.

Neutrophils contribute to excess serum BAFF levels and promote CD4+ T cell and B cell responses in lupus-prone mice.

Despite increased frequencies of neutrophils found in autoimmune diseases such as systemic lupus erythematosus (SLE), how they contribute to disease pathogenesis and the mechanisms that affect the accumulation of neutrophils are poorly understood. The aim of this study was to identify factors in autoantibody-mediated autoimmunity that controls the accumulation of spleen resident neutrophils and to determine whether neutrophils contribute to abnormal B cell responses. Increased levels of the cytokine BAFF have been linked to loss of B cell tolerance in autoimmunity, but the cellular source responsible for excess BAFF is unknown.

Mcl-1 is essential for the survival of plasma cells.

The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors.

Regulatory roles of the tumor necrosis factor receptor BCMA.

B cell maturation antigen (BCMA) is a tumor necrosis family receptor (TNFR) member that is predominantly expressed on terminally differentiated B cells and, upon binding to its ligands B cell activator of the TNF family (BAFF) and a proliferation inducing ligand (APRIL), delivers pro-survival cell signals. Thus, BCMA is mostly known for its functional activity in mediating the survival of plasma cells that maintain long-term humoral immunity. The expression of BCMA has also been linked to a number of cancers, autoimmune disorders, and infectious diseases that suggest additional roles for BCMA activity.

Optimized protocol for the isolation of spleen-resident murine neutrophils.

Neutrophils are an important cellular component of the innate immune system that provides immediate protection to the host from infection. Neutrophil infiltration into inflamed peripheral tissues during infection is beneficial for immunity through phagocytosis of microbes, the release of antimicrobial factors, and secretion of proinflammatory cytokines. Recent reports further suggest that spleen-infiltrating neutrophils play a role in the adaptive immune response by providing survival signals to B cells.

Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation.

The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN-dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known.