Systemic sclerosis (SSc) is characterized by tissue fibrosis and autoimmunity. Although the pathogenic relationship between autoimmunity and clinical manifestations of SSc remains unknown, SSc patients display abnormal immune responses including the production of disease-specific autoantibodies. Previous studies have demonstrated that B cells play a critical role in systemic autoimmunity and disease expression through various functions such as induction of the activation of other immune cells in addition to autoantibody production. CD19 is a crucial regulator of B cell activation. Recent studies demonstrated that B cells from SSc patients showed an up-regulated CD19 signaling pathway that induced SSc-specific autoantibody production in SSc mouse models. CD19 transgenic mice lost tolerance for autoantigen and generated autoantibodies spontaneously. B cells from SSc patients exhibited an overexpression of CD19 that induced SSc-specific autoantibody production in transgenic mice. Moreover, SSc patients displayed intrinsic B cell abnormalities characterized by chronic hyper-reactivity of memory B cells, which was possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a genetic model of SSc, showed augmented CD19 signaling. In bleomycin-induced SSc mouse models, endogenous ligands for toll-like receptor 4 induced by bleomycin stimulated B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, the loss of CD19 resulted in the inhibition of B cell hyper-reactivity and autoantibody production, which are associated with improvements in fibrosis and a parallel decrease in fibrogenic cytokine production by B cells. Taken together, the findings suggest that altered B cell function may result in tissue fibrosis as well as autoimmunity in SSc.
Animals ; Autoantibodies ; Autoimmunity ; B-Lymphocytes ; Bleomycin ; Cytokines ; Fibrosis ; Humans ; Ligands ; Lymphocyte Activation* ; Memory ; Mice ; Mice, Transgenic ; Models, Genetic ; Scleroderma, Systemic* ; Toll-Like Receptor 4

Strenuous exercise induces upper respiratory tract infection (URTI), whereas moderate exercise prevents URTI. This study aimed to assess the incidence of URTI and the association between URTI episodes and exercise duration in Japanese collegiate athletes. A cross-sectional survey was conducted with 1,740 participants; 1,235 responses were eligible for analysis. Participants were classified into three groups: control group (weekly total exercise duration <60 min, n=405), exercise group (weekly total exercise duration >60 min, n=193), and athlete group (joined a sports club and weekly exercise frequency >5 days, n=637). We requested the following information from participants: basic characteristics, incidence of URTI symptoms (fever, runny or plugged nose, sore throat, and cough) or influenza for each month over the past year, day of the week exercise is typically performed, and duration of exercise per week. The incidence of URTI episodes per year was significantly lower in the athlete group (2.0 ± 2.4 episodes) compared to the control group (2.6 ± 2.4 episodes, p<0.001). The incidence of URTI episodes did not significantly differ between the control group and exercise group (2.9 ± 2.9 episodes, p=0.607). Although the frequency of URTI episodes and exercise duration were not significantly associated among male athletes (p=0.209), they were positively associated in female athletes (p=0.027). These results indicate that Japanese collegiate athletes experience fewer URTI episodes than non-athletes, but athletes who exercise for long durations may frequently experience URTI, particularly female athletes.