Abstract
BackgroundThe incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains.MethodsYoung and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function.ResultsWhile the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo.ConclusionWhile old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.
Highlights
Elder people commonly exhibit a low-grade systemic, sterile inflammation, a phenomenon termed inflammaging [1]
While we detected no alteration of the overall CD90+CD45- Fibroblast-like synoviocytes (FLS) population between young and old mice at any time point investigated, we recovered less CD90-CD45- FLS from the small joints of non-immunized old mice compared to young mice (Fig. 1f)
We did not focus on FLS subpopulations in detail, that overall difference of CD90-CD45- FLS between young and old mice observed in naïve mice was no longer detectable at day 56 after arthritis induction (Fig. 1f)
Summary
Elder people commonly exhibit a low-grade systemic, sterile inflammation, a phenomenon termed inflammaging [1]. The identification has been refined to CD34-FAPα+NOTCH3+CD90+ FLS being located at the blood vessel of RA synovium, which differentiate from CD90- FLS population upon activation of Notch signaling [23,24,25] These pathogenic FLS attract and activate leukocytes to the synovial surrounding by production of large arrays of pro-inflammatory chemokines and cytokines like CCL2 and IL-6, respectively [23, 24]. It remains to be elucidated, whether how the homeostasis of these pathologic FLS is altered in elder individuals. We analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.