Postnatal administration of S-adenosylmethionine restores developmental AHR activation-induced deficits in CD8+ T cell function during influenza A virus infection.

Developmental exposures can influence life-long health; yet, counteracting negative consequences is challenging due to poor understanding of cellular mechanisms. The aryl hydrocarbon receptor (AHR) binds many small molecules, including numerous pollutants. Developmental exposure to the signature environmental AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly dampens adaptive immune responses to influenza A virus (IAV) in adult offspring.

Glucagon-receptor-antagonism-mediated β-cell regeneration as an effective anti-diabetic therapy.

Type 1 diabetes mellitus (T1D) is a chronic disease with potentially severe complications, and β-cell deficiency underlies this disease. Despite active research, no therapy to date has been able to induce β-cell regeneration in humans. Here, we discover the β-cell regenerative effects of glucagon receptor antibody (anti-GcgR).

The Ancestral Environment Shapes Antiviral CD8 T cell Responses across Generations.

Recent studies have linked health fates of children to environmental exposures of their great grandparents. However, few studies have considered whether ancestral exposures influence immune function across generations. Here, we report transgenerational inheritance of altered T cell responses resulting from maternal (F0) exposure to the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Environmental cues received during development shape dendritic cell responses later in life.

Environmental signals mediated via the aryl hydrocarbon receptor (AHR) shape the developing immune system and influence immune function. Developmental exposure to AHR binding chemicals causes persistent changes in CD4+ and CD8+ T cell responses later in life, including dampened clonal expansion and differentiation during influenza A virus (IAV) infection. Naïve T cells require activation by dendritic cells (DCs), and AHR ligands modulate the function of DCs from adult organisms.

Data on the histological and immune cell response in the popliteal lymph node in mice following exposure to metal particles and ions.

Hip implants containing cobalt-chromium (CoCr) have been used for over 80 years. In patients with metal-on-metal (MoM) hip implants, it has been suggested that wear debris particles may contribute to metal sensitization in some individuals, leading to adverse reactions. This article presents data from a study in which the popliteal lymph node assay (PLNA) was used to assess immune responses in mice treated with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3, and NiCl2) or Cr2O3 particles with metal salts ("A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay" (B.

A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay.

The objective of this preliminary study was to evaluate the threshold for immune stimulation in mice following local exposure to metal particles and ions representative of normal-functioning cobalt-chromium (CoCr) metal-on-metal (MoM) hip implants. The popliteal lymph node assay (PLNA) was used in this study to assess immune responses in BALB/c mice following treatment with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3 and NiCl2), or Cr2O3 particles together with metal salts using single-dose exposures representing approximately 10days (0.000114mg), 19years (0.

The toxicity of crude 4-methylcyclohexanemethanol (MCHM): review of experimental data and results of predictive models for its constituents and a putative metabolite.

Crude 4-methylcyclohexanemethanol (MCHM) is an industrial solvent used to clean coal. Approximately 10 000 gallons of a liquid mixture containing crude MCHM were accidently released into the Elk River in West Virginia in January 2014. Because of the proximity to a water treatment facility, the contaminated water was distributed to approximately 300 000 residents.

Activation of the aryl hydrocarbon receptor during development enhances the pulmonary CD4+ T-cell response to viral infection.

Respiratory infections are a threat to health and economies worldwide, yet the basis for striking variation in the severity of infection is not completely understood. Environmental exposures during development are associated with increased severity and incidence of respiratory infection later in life. Many of these exposures include ligands of the aryl hydrocarbon receptor (AHR), a transcription factor expressed by immune and nonimmune cells.

Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+ T cell responses.

Successfully fighting infection requires a properly tuned immune system. Recent epidemiological studies link exposure to pollutants that bind the aryl hydrocarbon receptor (AHR) during development with poorer immune responses later in life. Yet, how developmental triggering of AHR durably alters immune cell function remains unknown.

Effects of developmental activation of the AhR on CD4+ T-cell responses to influenza virus infection in adult mice.

Background: Epidemiological and animal studies indicate that maternal exposure to pollutants that bind the aryl hydrocarbon receptor (AhR) correlates with poorer ability to combat respiratory infection and lower antibody levels in the offspring. These observations point to an impact on CD4+ T cells. Yet, the consequence of developmental exposure to AhR ligands on the activation and differentiation of CD4+ T cells has not been directly examined.

New insights into the role of the aryl hydrocarbon receptor in the function of CD11c⁺ cells during respiratory viral infection.

The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4(+) cell lineage development and function. It also regulates antiviral CD8(+) T-cell responses, but via indirect mechanisms that have yet to be determined. Here, we show that during acute influenza virus infection, AHR activation skews dendritic-cell (DC) subsets in the lung-draining lymph nodes, such that there are fewer conventional CD103(+) DCs and CD11b(+) DCs.

Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease?

There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body's first line of defense.

Vascular gene expression patterns are conserved in primary and metastatic brain tumors.

Malignant primary glial and secondary metastatic brain tumors represent distinct pathological entities. Nevertheless, both tumor types induce profound angiogenic responses in the host brain microvasculature that promote tumor growth. We hypothesized that primary and metastatic tumors induce similar microvascular changes that could function as conserved angiogenesis based therapeutic targets.

Characterization of TEM1/endosialin in human and murine brain tumors.

Background: TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models.

Methods: In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays.

Plasmalemmal vesicle associated protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models.

Background: Plasmalemmal vesicle associated protein-1 (PV-1) is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS) diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state.

Results: We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain.