Girl power: estrogen promotes HSC self-renewal.

Although some hematopoietic cell types are known to respond to sex hormones, hematopoietic stem cells (HSCs) are generally thought to function similarly in both sexes. Recently in Nature, Nakada et al. (2014) show that HSCs respond to higher levels of estrogen in females, resulting in enhanced self-renewal and increased erythropoiesis.

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region.

BANK1 controls CpG-induced IL-6 secretion via a p38 and MNK1/2/eIF4E translation initiation pathway.

BANK1, an adaptor protein expressed in B cells, plays a little understood role in B cell signaling. Because BANK1 contains an N-terminal putative Toll/IL-1R receptor domain, we used mouse Bank1(-/-) splenic B cells to test whether BANK1 affects signaling induced by the TLR9 agonist CpG. Following CpG stimulation, BANK1 deficiency reduced p38 phosphorylation without affecting that of ERK or JNK and reduced IL-6 secretion.

When killers become helpers.

Interplay between a natural killer (NK)-cell receptor, NKp30, and other cells in the salivary glands profoundly affects pathogenesis of the autoimmune disease Sjögren's syndrome (Rusakiewicz et al., this issue).

Autoimmunity and infection in Sjögren's syndrome.

Purpose Of Review: To summarize the recent developments concerning the potential viral pathomechanisms and involvement of viruses in Sjögren's syndrome, and to highlight the areas for future research and therapies.

Recent Findings: Activated IFN-1 pathway plays an important part in the autoimmune disease process of Sjögren's syndrome; therefore, several therapies aiming to reduce or inhibit the IFN-1 production and its effects may be a target for future treatment plans. Activated aryl hydrocarbon receptor may interact with latent Epstein-Barr virus (EBV) infection, which in turn may predispose to the development of Sjögren's syndrome.

GFP affects human T cell activation and cytokine production following in vitro stimulation.

There are many Green Fluorescent Proteins (GFPs) originating from diverse species that are invaluable to cell biologists today because of their ability to provide experimental visualization of protein expression. Since their initial discovery, they have been modified and improved to provide more stable variants with emission ranges spanning a wide array of colors. Due to their ease of expression both in-vitro and in-vivo, they are an attractive choice for use as markers in molecular biology.

Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse.

Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis.

Stochastic humoral immunity to Bacillus anthracis protective antigen: identification of anti-peptide IgG correlating with seroconversion to Lethal Toxin neutralization.

A substantial fraction of individuals vaccinated against anthrax have low to immeasurable levels of serum Lethal Toxin (LeTx)-neutralizing activity. The only known correlate of protection against Bacillus anthracis in the currently licensed vaccine is magnitude of the IgG response to Protective Antigen (PA); however, some individuals producing high serum levels of anti-PA IgG fail to neutralize LeTx in vitro. This suggests that non-protective humoral responses to PA may be immunodominant in some individuals.

MHC class II and non-MHC class II genes differentially influence humoral immunity to Bacillus anthracis lethal factor and protective antigen.

Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles.

IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation.

Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b(+) splenic DC. We found that the skin of naive IRF4(-/-) mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b(+) and CD103(+) dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency.

Mapping susceptibility gene in systemic lupus erythematosus.

Genome-wide association studies have identified many dozen genetic intervals that harbor single-nucleotide polymorphisms (SNPs) showing statistical association with systemic lupus erythematosus. Despite the wealth of data produced, there are limitations of these studies. The causal alleles at a given locus are not identified; only SNP is strong linkage disequilibrium with the putative causative alleles.

WITHDRAWN: A female autoimmunity gene exists: DDX3X.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.

Induction of anti-Ro60/anti-La by immunisation with spectrin and induction of anti-spectrin by immunisation with Ro60 and 4-hydroxy-2-nonenal-modified Ro60 immunisation.

Objectives: The Ro ribonucleoprotein particle, targeted in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), includes Ro60 (SSA) and La (SSA) autoantigens. Anti-Ro60 occurs in SLE and SS. The importance of α-fodrin and spectrin as well as anti-Ro and anti-fodrin/spectrin antibodies in SS and SLE, led us to hypothesise that rabbit immunisation with Ro60 or 4-hydroxy-2-nonenal-modified Ro60 would induce anti-spectrin.

Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions.

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype.

Putative sequences on Ro60 three-dimensional structure accessible for 4-hydroxy-2-nonenal (HNE) modification compared to in vitro HNE modification of Ro60 sequences.

We have previously reported accelerated acquisition of new autoreactivity upon immunization with 4-hydroxy-2-nonenal (HNE)-modified Ro60, as well as differential induction of lupus or Sjögren's syndrome by immunization with Ro60 containing varying amounts of HNE. Since the number of HNE molecules on Ro60 appears to be important, we hypothesized that specific sequences on Ro60 are targets for HNE-modification. Using surface plasmon resonance (SPR) we have also shown intramolecular protein-protein interaction between Ro60 and Ro multiple antigenic peptides (MAPs).

Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci.

Toll-like receptors in systemic lupus erythematosus: potential targets for therapeutic intervention.

Toll-like receptors (TLRs) have attracted increased attention in recent years, not only for their role in sensing conserved microbial components, but also in the realm of autoimmunity. Although TLRs are most widely known for their capacity to detect conserved motifs of infectious agents, mounting evidence indicates that these innate receptors also promote autoimmune conditions by causing uncontrolled autoinflammation as a result of chronic recognition of self. In response to the need for modern approaches to treatment of autoimmune diseases, several groups have begun investigating ways to target TLRs as new therapeutic options for autoimmune conditions.

The role of epigenetic variation in the pathogenesis of systemic lupus erythematosus.

The focus of the present review is on the extent to which epigenetic alterations influence the development of systemic lupus erythematosus. Lupus is a systemic autoimmune disease characterized by the production of autoantibodies directed at nuclear self-antigens. A DNA methylation defect in CD4+ T cells has long been observed in idiopathic and drug-induced lupus.

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.

Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus.

Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren syndrome or systemic lupus erythematosus in BALB/c mice.

Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used.