Synovitis is common in patients with osteoarthritis (OA) and is associated with pain and disease progression. We have previously demonstrated that the chemokine C-C motif chemokine 22 (CCL22) induces chondrocyte apoptosis however, the effects of CCL22 on the synovium remain unknown. Therefore, our goal was to investigate the effect of CCL22 on fibroblast-like synoviocytes (FLS). CCL22 treatment suppressed expression of IL-4 and IL-10 and promoted expression of S100A12 in FLS. The response of FLS to CCL22 was not dependent on the disease state of the joint (e.g., normal versus OA), but was instead correlated with the individuals' synovial fluid level of CCL22. CCL22 induction of S100A12 in FLS was attenuated after knockdown of CCR3, yet ligands of CCR3 (CCL7, CCL11) did not induce S100A12 expression. In the presence of CCL22, CCR3-positive FLS upregulate CCL22 and S100A12 driving a potential feedforward pro-inflammatory mechanism distinct from canonical CCL22 and CCR3 pathways.
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http://dx.doi.org/10.1016/j.isci.2020.101943 | DOI Listing |
Allergy
January 2025
School of Immunology and Microbial Sciences, King's College London, London, UK.
Background: Alarmin cytokine IL-25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL-25 remain poorly defined.
Objective: To investigate induction and expression of IL-25 receptor (IL-17RB) by B cells and evaluate responsiveness of IL-17RB-expressing B cells to IL-25 in vitro.
J Clin Invest
January 2025
Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Artificial Intelligence Research Center, Institute of Information Technologies, Mathematics and Mechanics, Lobachevsky State University, 603022 Nizhny Novgorod, Russia.
Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near -40 °C and the minimum below -60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to their Central Russian counterparts, residing in a considerably milder climate. In this paper, we analyzed these cohorts from the inflammaging perspective and addressed two hypotheses: a mismatch in the immunological profiles and accelerated inflammatory aging in Yakuts.
View Article and Find Full Text PDFAllergy
January 2025
Department of Dermatology, Icahn School of Medicine at the Mount Sinai, New York, New York, USA.
Introduction: Chronic hand eczema (CHE) is a highly prevalent inflammatory skin condition which is often resistant to conventional treatments. Molecular insights of CHE remain limited. Tape stripping combined with high-throughput RNA sequencing can now provide a better insight into CHE pathogenesis in a minimally invasive fashion.
View Article and Find Full Text PDFOccup Environ Med
January 2025
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland, USA
Background: Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin.
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