Osteoimmunological interations at the switch from acute to chronic arthritis

Böttcher, Martin

Immunization with Glucose-6-phosphate isomerase induces arthritis in susceptible strains of mice. Depletion of regulatory T cells prior to immunization switches the usually acute, self-limiting course to a non-remitting, destructive arthritis. This provides a possibility to study molecular switches for this transition within one mouse model. To examine the role of fibroblast-like synoviocytes (FLS), which are known to modulate immune responses via the production of inflammatory mediators, the phenotype and function of FLS from mice with either acute, self-limiting or non-remitting, destructive arthritis was studied. The cellular composition of isolates and cultured cells was found to be stably comprised mainly of fibroblasts and fibrocytes. The secretion of cytokines and chemokines did not differ significantly between FLS from nondepleted and Treg-depleted mice after in vitro stimulation. Furthermore, the secretion and activity of matrix metalloproteases was enhanced in the FLS from mice with chronic arthritis compared to samples from the ones with the acute form. Additional functional differences include the collagen-destructive potential and the potential to attach and eventually invade wild type cartilage. Here, FLS from Treg-depleted chronic arthritic mice showed a higher invasive and destructive potential. This aggressive phenotype could be reversed by the preventive and therapeutic treatment of the animals with anti-IL-17A. Ultimately, FLS from Treg-depleted mice were able to destroy cartilage and bone in vivo upon transfer into immunodeficient mice. The results are compatible with the hypothesis that uninhibited inflammation in the early phase of Treg-depleted mice causes the acquisition of an autonomously aggressive phenotype of synoviocytes mediated via IL-17 which contributes to the switch from acute to chronic arthritis even in the absence of late support from T and B lymphocytes.

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Böttcher, Martin: Osteoimmunological interations at the switch from acute to chronic arthritis. 2015.

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