YAP, but Not RSPO-LGR4/5, Signaling in Biliary Epithelial Cells Promotes a Ductular Reaction in Response to Liver Injury.

Biliary epithelial cells (BECs) form bile ducts in the liver and are facultative liver stem cells that establish a ductular reaction (DR) to support liver regeneration following injury. Liver damage induces periportal LGR5+ putative liver stem cells that can form BEC-like organoids, suggesting that RSPO-LGR4/5-mediated WNT/β-catenin activity is important for a DR. We addressed the roles of this and other signaling pathways in a DR by performing a focused CRISPR-based loss-of-function screen in BEC-like organoids, followed by in vivo validation and single-cell RNA sequencing.

GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

Background: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown.

Methods: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1 ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD).

CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells.

Psoriatic skin lesions are characterized by an inflammatory infiltrate, consisting of dendritic cells, monocytes, and both CD4(+) and CD8(+) T lymphocytes. Although the chemokines involved in the migration of CD4(+) T cells into psoriatic skin are well characterized, those regulating CD8(+) T-cell recruitment are less understood. We found that the percentages of peripheral blood CD8(+) T cells expressing CXCR6 were higher in psoriatic patients than in healthy or atopic individuals.

CCL18 is expressed in patients with bullous pemphigoid and parallels disease course.

Background: The autoimmune skin disease bullous pemphigoid (BP) is characterized by subepidermal blister formation and a strong dermal infiltrate of mononuclear cells and eosinophils as well as a T-helper (Th) 2-dominated cytokine milieu. CCL18 is a chemokine, with unknown receptor counterpart, frequently associated with inflammatory Th2-type responses.

Objectives: The study was performed to investigate an association of CCL18 with BP.

Triggering the succinate receptor GPR91 on dendritic cells enhances immunity.

Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines.