Seeing the Confetti Colors in a New Light Utilizing Flow Cytometry and Imaging Flow Cytometry.

Stochastic multicolor transgenic labeling systems, such as the Brainbow reporters, have emerged as powerful tools in lineage tracing experiments. Originally designed for large-scale mapping of neuronal projections in densely populated tissues, they have been repurposed for diverse uses. The Brainbow 2.

Interrogating Individual Autoreactive Germinal Centers by Photoactivation in a Mixed Chimeric Model of Autoimmunity.

Autoimmune diseases present a significant health burden. Fundamental questions regarding the development and progression of autoimmune disease remain unanswered. One requirement for advancements in our understanding of the underlying disease mechanisms and cellular dynamics is the precise coupling of the microanatomical location of cell subsets with downstream molecular or functional analyses; a goal that has traditionally been difficult to achieve.

Chronic Active Arthritis Driven by Macrophages Without Involvement of T Cells: A Novel Experimental Model of Rheumatoid Arthritis.

Objective: To develop a new chronic rheumatoid arthritis model that is driven by the innate immune system.

Methods: Injection of a cocktail of 4 monoclonal antibodies against type II collagen, followed on days 5 and 60 by intraperitoneal injections of mannan (from Saccharomyces cerevisiae), was used to induce development of chronic arthritis in B10.Q mice.

The Macrophage Mannose Receptor Regulate Mannan-Induced Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis-Like Disease Models.

The injection of mannan into mice can result in the development of psoriasis (Ps) and psoriatic arthritis (PsA), whereas co-injection with antibodies toward collagen type II leads to a chronic rheumatoid-like arthritis. The critical event in all these diseases is mannan-mediated activation of macrophages, causing more severe disease if the macrophages are deficient in neutrophil cytosolic factor 1 (Ncf1), i.e.

Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage.

Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic.

Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms.

Aims: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis.

(18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.

Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.

Direct Comparison of a Natural Loss-Of-Function Single Nucleotide Polymorphism with a Targeted Deletion in the Ncf1 Gene Reveals Different Phenotypes.

The genetic targeting of mouse models has given insight into complex processes. However, phenotypes of genetically targeted mice are susceptible to artifacts due to gene manipulation, which may lead to misinterpretation of the observations. To directly address these issues, we have compared the immunological phenotypes of Ncf1 knockout mice with Ncf1m1J mice possessing a naturally occurring intronic loss-of-function SNP in their Ncf1 gene.

Hydrogen peroxide as an immunological transmitter regulating autoreactive T cells.

Significance: An unexpected finding, revealed by positional cloning of genetic polymorphisms controlling models for rheumatoid arthritis, exposed a new function of Ncf1 and NADPH oxidase (NOX) 2 controlled oxidative burst.

Recent Advances: A decreased capacity to produce ROS due to a natural polymorphism was found to be the major factor leading to more severe arthritis and increased T cell-dependent autoimmunity.

Critical Issues: In the vein of this finding, we here review a possible new role of ROS in regulating inflammatory cell and autoreactive T cell activity.