How does the microbiota control systemic innate immunity?

The intestinal microbiota has a pervasive influence on mammalian innate immunity fortifying defenses to infection in tissues throughout the host. How intestinal microbes control innate defenses in systemic tissues is, however, poorly defined. In our opinion, there are three core challenges that need addressing to advance our understanding of how the intestinal microbiota controls innate immunity systemically: first, deciphering how signals from intestinal microbes are transmitted to distal tissues; second, unraveling how intestinal microbes prime systemic innate immunity without inducing widespread immunopathology; and third, identifying which intestinal microbes control systemic immunity.

Symbiotic Firmicutes establish mutualism with the host via innate tolerance and resistance to control systemic immunity.

The intestinal microbiota regulates immunity across organ systems. Which symbionts control systemic immunity, the mechanisms they use, and how they avoid widespread inflammatory damage are unclear. We uncover host tolerance and resistance mechanisms that allow Firmicutes from the human microbiota to control systemic immunity without inducing immunopathology.

Protein tyrosine phosphatase PTPN22 is dispensable for dendritic cell antigen processing and promotion of T-cell activation by dendritic cells.

The PTPN22R620W single nucleotide polymorphism increases the risk of developing multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the expression of the murine disease associated variant orthologue (Ptpn22R619W) is reported to dysregulate pattern recognition receptor signalling in dendritic cells (DCs) and promote T-cell proliferation. Because T-cell activation is dependent on DC antigen uptake, degradation and presentation, we analysed the efficiency of these functions in splenic and GM-CSF bone marrow derived DC from wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice.

Protein tyrosine phosphatase PTPN22 regulates IL-1β dependent Th17 responses by modulating dectin-1 signaling in mice.

A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno-receptors. Fungal β-glucan receptor dectin-1 signals via Syk, and dectin-1 stimulation induces arthritis in mouse models.

DNA methylation governs the dynamic regulation of inflammation by apoptotic cells during efferocytosis.

Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity.

Engulfment of activated apoptotic cells abolishes TGF-β-mediated immunoregulation via the induction of IL-6.

Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β.

Evolution of the magnetic field structure of the Crab pulsar.

Pulsars are highly magnetized rotating neutron stars and are well known for the stability of their signature pulse shapes, allowing high-precision studies of their rotation. However, during the past 22 years, the radio pulse profile of the Crab pulsar has shown a steady increase in the separation of the main pulse and interpulse components at 0.62° ± 0.

Telemedicine and Pediatric Obesity Treatment: Review of the literature and lessons learned.

Pediatric obesity is more prevalent in rural areas, yet rural families may not have access to pediatric obesity treatment programs. Use of new technologies, particularly telemedicine, has proven effective in other behavioral fields, such as psychiatry. This paper reviews the literature on the use of telemedicine in pediatric obesity treatment, and describes one tertiary-care pediatric obesity telemedicine program.

TeleFIT: adapting a multidisciplinary, tertiary-care pediatric obesity clinic to rural populations.

Pediatric obesity occurs most frequently in underserved communities where families have difficulty accessing healthcare. Disproportionate obesity rates in rural children denote significant disparities warranting innovative solutions. However, intensive, tertiary-care treatment options outlined in recent expert recommendations may not be available to families living in rural areas.