Search

Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody-producing B cells. Activation of B cells is maintained within ectopic germinal centres found in affected joints. Fibroblast-like synoviocytes (FLS) present in inflamed joints support B-cell survival, activation, and differentiation. CD27+ memory B cells and naive B cells show very different responses to activation, particularly by CD40 ligand (CD40L). We show that FLS-dependent activation of human B cells is dependent on interleukin-6 (IL-6) and CD40L. FLS have been shown to activate both naive and memory B cells. Whether the activating potential of FLS is different for naive and memory B cells has not been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are able to induce plasma cell differentiation, isotype switching, and antibody production in memory B cells, the ability of FLS to activate naive B cells is significantly lower., (© 2024 The Author(s). Immunology published by John Wiley & Sons Ltd.)

In recent years, the role of sympathetic nervous fibers in chronic inflammation has become increasingly evident. At the onset of inflammation, sympathetic activity is increased in the affected tissue. However, sympathetic fibers are largely absent from chronically inflamed tissues. Apparently, there is a very dynamic relationship between sympathetic innervation and the immune system in areas of inflammation, and hence a rapid and easy method for quantification of nerve fiber density of target organs is of great value to answer potential research questions. Sympathetic nerve ends lie in close proximity to immune cells in lymphoid tissues and lymphoid cells are equipped with catecholamine receptors. Catecholamines such as dopamine and adrenaline are secreted by sympathetic nervous fibers and can influence immune cell activity directly. Thereby the sympathetic nervous system immediately participates in the regulation of inflammation. Changes in innervation density could therefore indicate dysregulation of inflammatory processes. Currently, nervous fiber densities are either determined by tedious manual counting, which is not suitable for high throughput approaches, or by expensive automated processes relying on specialized software and high-end microscopy equipment. Usually, tyrosine hydroxylase (TH) is used as the marker for sympathetic fibers. In order to overcome the current quantification bottleneck with a cost-efficient alternative, an automated process was established and compared to the classic manual approach of counting TH-positive sympathetic fibers. Since TH is not exclusively expressed on sympathetic fibers, but also in a number of catecholamine-producing cells, a prerequisite for automated determination of fiber densities is to reliably distinguish between cells and fibers. Therefore, an additional stain using peripherin which is exclusively expressed in nervous fibers as a secondary marker was established. This new and simple method can be used as a high-throughput approach to reliably and quickly estimate sympathetic nervous system (SNS) nerve fiber density in target tissues., (Copyright © 2019 The Authors; exclusive licensee Bio-protocol LLC.)

In recent years, the role of sympathetic nervous fibers in chronic inflammation has become increasingly evident. At the onset of inflammation, sympathetic activity is increased in the affected tissue. However, sympathetic fibers are largely absent from chronically inflamed tissue. Apparently, there is a very dynamic relationship between sympathetic innervation and the immune system in areas of inflammation, and hence a rapid and easy method for quantification of nerve fiber density of target organs is of great value to answer potential research questions. Currently, nervous fiber densities are either determined by tedious manual counting, which is not suitable for high throughput approaches, or by expensive automated processes relying on specialized software and high-end microscopy equipment. Usually, tyrosine hydroxylase (TH) is used as the marker for sympathetic fibers. In order to overcome the current quantification bottleneck with a cost-efficient alternative, an automated process was established and compared to the classic manual approach of counting TH-positive sympathetic fibers. Since TH is not exclusively expressed on sympathetic fibers, but also in a number of catecholamine-producing cells, a prerequisite for automated determination of fiber densities is to reliably distinct between cells and fibers. Therefore, an additional staining using peripherin exclusively expressed in nervous fibers as a secondary marker was established. Using this novel approach, we studied the spleens from a syndecan-3 knockout (SDC3KO) mouse line, and demonstrated equal results on SNS fiber density for both manual and automated counts (Manual counts: wildtype: 22.57 +/- 11.72 fibers per mm2; ko: 31.95 +/- 18.85 fibers per mm2; p = 0.05; Automated counts: wildtype: 31.6 +/- 18.98 fibers per mm2; ko: 45.49 +/- 19.65 fibers per mm2; p = 0.02). In conclusion, this new and simple method can be used as a high-throughput approach to reliably and quickly estimate SNS nerve fiber density in target tissues., Competing Interests: The authors have declared that no competing interests exist.

Waste management procedures in developing countries are associated with occupational safety and health risks. Gastro-intestinal infections, respiratory and skin diseases as well as muscular-skeletal problems and cutting injuries are commonly found among waste workers around the globe. In order to find efficient, sustainable solutions to reduce occupational risks of waste workers, a methodological risk assessment has to be performed and counteractive measures have to be developed according to an internationally acknowledged hierarchy. From a case study in Addis Ababa, Ethiopia suggestions for the transferral of collected household waste into roadside containers are given. With construction of ramps to dump collected household waste straight into roadside containers and an adaptation of pushcarts and collection procedures, the risk is tackled at the source., (Copyright © 2012 Elsevier Ltd. All rights reserved.)