Adenosine, bridging chronic inflammation and tumor growth.

Adenosine (Ado) is a well-known immunosuppressive agent that may be released or generated extracellularly by cells, via degrading ATP by the sequential actions of the ectonucleotides CD39 and CD73. During inflammation Ado is produced by leukocytes and tissue cells by different means to initiate the healing phase. Ado downregulates the activation and the effector functions of different leukocyte (sub-) populations and stimulates proliferation of fibroblasts for re-establishment of intact tissues.

Guidelines for mouse and human DC functional assays.

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. Recent studies have provided evidence for an increasing number of phenotypically distinct conventional DC (cDC) subsets that on one hand exhibit a certain functional plasticity, but on the other hand are characterized by their tissue- and context-dependent functional specialization. Here, we describe a selection of assays for the functional characterization of mouse and human cDC.

Tolerance to 2,4-Dinitrofluorobenzene‒Induced Contact Hypersensitivity Is Mediated by CD73-Expressing Tissue-Homing Regulatory T Cells.

Regulatory T cells (Tregs) express CD73, an ectonucleotidase that converts adenosine (Ado) monophosphate to Ado, which has been shown to suppress immune reactions. To investigate the role(s) of CD73 Tregs during the induction of tolerance, we used a 2,4-dinitrofluorobenzene‒driven contact hypersensitivity model, in which tolerance can be induced by pretreating wild type mice with 2,4-dinitrothiocyanobenzene. CD73-deficient mice were unable to acquire tolerance.

Impaired Treg-DC interactions contribute to autoimmunity in leukocyte adhesion deficiency type 1.

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare disease resulting from mutations in the gene encoding for the common β-chain of the β2-integrin family (CD18). The most prominent clinical symptoms are profound leukocytosis and high susceptibility to infections. Patients with LAD-1 are prone to develop autoimmune diseases, but the molecular and cellular mechanisms that result in coexisting immunodeficiency and autoimmunity are still unresolved.