The immunological role of the spleen in autoimmune arthritis: lessons from mice with genetic spleen disorganisation or splenectomy.

The spleen is a major secondary lymphoid organ with diverse functions, such as participating in the homeostasis of the intraperitoneal cavity leukocytes, B cell maturation, innate immune response against foreign antigens, and adaptive immunity. In the context of autoimmune diseases, specifically RA, splenomegaly is a common observation, indicating a direct involvement in RA pathogenesis in humans and mice. In this review, our aim was to shed light, at least partially, on the immunological role of the spleen in the development and pathogenesis of RA using a mouse autoimmune arthritis model. Herein we summarize our recent results from mice with severely disturbed spleen structure due to Nkx2-3 deficiency, and from mice which were splenectomized at different stages of arthritis induction. The anatomical defects of spleen in the Nkx2-3-/- mice affected the B cells activation, which might have resulted in ameliorated autoimmune arthritis. In case of surgical splenectomy prior to autoimmune arthritis induction other components of the immune network compensated for the spleen and arthritis developed similar to control mice however with slightly different immunological background. Importantly, splenectomy in the early stages of autoimmune arthritis (i.e. during the process of autoimmune arthritis induction) had a significant protective effect against the articular bone and cartilage damage. Collectively the spleen influences significantly the level of pro-inflammatory cytokines and autoantibodies in the blood serum and shifts the immune response towards Th1 dominance. These data indicate that the spleen is indeed involved in the development of autoimmune arthritis. [ABSTRACT FROM AUTHOR]