Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

Abstract

Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study

“…Secondly, the intermediary roles played by specific immune cell markers in this association were observed. While B cells play a pivotal role in RA pathogenesis by producing autoantibodies, studies in collagen antibody-induced arthritis mice revealed no significant changes in B cell numbers within the TMJ compared to control mice ( 11 ). However, a notable increase in T cells was observed in TMJ when mechanical stress was applied to the mandibular condyle, suggesting their potential involvement in RA-associated TMDs ( 11 ).…”

“…While B cells play a pivotal role in RA pathogenesis by producing autoantibodies, studies in collagen antibody-induced arthritis mice revealed no significant changes in B cell numbers within the TMJ compared to control mice ( 11 ). However, a notable increase in T cells was observed in TMJ when mechanical stress was applied to the mandibular condyle, suggesting their potential involvement in RA-associated TMDs ( 11 ). Our results suggest that the impact of RA on TMDs may be mediated through reduced CD3 expression on CD4 T cells in serum and an elevated percentage of CD25++ CD8+ T cells.…”

“…Numerous studies have reported elevated TMDs prevalence in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and multiple sclerosis (MS) compared with healthy individuals ( 7 – 9 ). Notably, robust evidence, including meta-analysis, imaging studies, and animal experiments, supports a strong association between RA and TMDs ( 6 , 10 , 11 ). The involvement of the TMJ in RA patient may follow similar destruction patterns as in other joints, such as synovial hyperemia, lymphocyte infiltration, bone degeneration, and fibrous adhesion ( 12 ).…”