Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles.

Virus-like nanoparticles (VNP) are regarded as efficient vaccination platforms and have proven to be useful for the non-anaphylactogenic delivery of allergen-specific immunotherapy in preclinical models previously. Herein, we sought to determine the mode of VNP uptake by antigen presenting cells (APC). Accordingly, we screened a collection of substances known to inhibit different uptake pathways by APC.

The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling.

T follicular helper (Tfh) cells are essential for the development of germinal center B cells and high-affinity antibody-producing B cells in humans and mice. Here, we identify the guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator of Tfh generation. Loss of Rinl leads to an increase of Tfh in aging, upon in vivo immunization and acute LCMV Armstrong infection in mice, and in human CD4+ T cell in vitro cultures.

24-Norursodeoxycholic acid reshapes immunometabolism in CD8 T cells and alleviates hepatic inflammation.

Background & Aims: 24-Norursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid used to treat immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC), where dysregulated T cells including CD8 T cells contribute to hepatobiliary immunopathology. We hypothesized that NorUDCA may directly modulate CD8 T cell function thus contributing to its therapeutic efficacy.

Methods: NorUDCA's immunomodulatory effects were first studied in Mdr2 mice, as a cholestatic model of PSC.

Blocking pannexin1 reduces airway inflammation in a murine model of asthma.

Stressed or injured cells release ATP into the extracellular milieu via the pannexin1 (Panx1) channels, which is the basis of inflammation in a variety of conditions, including allergic lung inflammation. Although the role of Panx1 in mediating inflammation has been well established, the role of its mimetic peptide, Panx1, which inhibits ATP release from Panx1 channels, in allergic asthma remains understudied. The aim of this study was to evaluate the effects of using Panx1 to inhibit Panx1 channel in a murine model of ovalbumin (OVA)-induced asthma.