A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family.

Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment.

Background & Aims: Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored.

Fingerprints of CD8+ T cells on human pre-plasma and memory B cells.

Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material.

Human CD180 Transmits Signals via the PIM-1L Kinase.

Toll-like receptors (TLRs) are important sensors of the innate immune system that recognize conserved structural motifs and activate cells via a downstream signaling cascade. The CD180/MD1 molecular complex is an unusual member of the TLR family, since it lacks the components that are normally required for signal transduction by other TLRs. Therefore the CD180/MD 1 complex has been considered of being incapable of independently initiating cellular signals.

Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis.

Background: In allergic diseases, like in rhinitis, antigen challenge induces rapid degranulation of tissue resident mast cells and subsequent recruitment of leukocytes in response to soluble immunmodulators. The fate of mast cell-derived, membrane associated factors in inflamed tissue remained however unresolved.

Methods: Components of the mast cell granular membrane, including the unique marker CD63var, were examined by FACS and by confocal laser scanning microscopy in cell culture and in diseased human tissue.