Migratory CD103CD11b cDC2s in Peyer's patches are critical for gut IgA responses following oral immunization.

Induction and regulation of specific intestinal immunoglobulin (Ig)A responses critically depend on dendritic cell (DC) subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of cluster of differentiation (CD)103 conventional DC (cDC)2s and lysozyme-expressing DC (LysoDCs) in the subepithelial dome and of CD103 cDC2s that expressed CD101 in the T cell zones, while oral ovalbumin (OVA) tolerization was instead associated with greater accumulation of cDC1s and peripherally induced regulatory T cells (pTregs) in this area. Decreased IgA responses were observed after CT-adjuvanted immunization in huCD207DTA mice lacking CD103 cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3 mice.

Vaccination with attachment proteins protects against gastric cancer.

Most cases of gastric cancer are caused by chronic infection, but the lack of early onco-diagnostics and a high risk for antibiotic resistance hampers early intervention through eradication of infection by antibiotics. We reported on a protective mechanism where gastric mucosal attachment can be reduced by natural antibodies that block the binding of its attachment protein BabA. Here we show that challenge infection with induced response of such blocking antibodies in both human volunteers and in rhesus macaques, that mucosal vaccination with BabA protein antigen induced blocking antibodies in rhesus macaques, and that vaccination in a mouse model induced blocking antibodies that reduced gastric mucosal inflammation, preserved the gastric juice acidity, and fully protected the mice from gastric cancer caused by .

The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation.

Germinal center (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fiber (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrecβCCL19gp38 fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin α5 (), pre-Tfh-cells, B-cells and DCs are displaced from follicle borders, correlating with fewer Tfh-cells and GC B-cells.

Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells.

Curative therapies against autoimmune diseases are lacking. Indeed, most of the currently available treatments are only targeting symptoms. We have developed a novel strategy for a therapeutic vaccine against autoimmune diseases based on intranasal administration of a fusion protein tolerogen, which consists of a mutant, enzymatically inactive, cholera toxin A1 (CTA1)-subunit genetically fused to disease-relevant high-affinity peptides and a dimer of D-fragments from protein A (DD).