Lymphocytes Are Not Required for Neurogenic Heterotopic Ossification Development after Spinal Cord Injury

Neurogenic heterotopic ossifications (NHOs) are incapacitating complications of traumatic brain and spinal cord injuries (SCI) that manifest as abnormal bone formation in periarticular muscles. Using a unique model of NHO after SCI in genetically unmodified mice, we have previously established that the innate immune system plays a key driving role in NHO pathogenesis. The role of adaptive immune cells in NHO pathogenesis, however, remains unexplored in this model. Here we established that B lymphocytes were reduced in the spleen and blood after SCI and increased in muscles of mice in which NHO develops, whereas minimal changes in T cell frequencies were noted. Interestingly, Rag1(-/-) mice lacking mature T and B lymphocytes, developed NHO, similar to wild-type mice. Finally, mice that underwent splenectomy before SCI and muscle damage also developed NHO to the same extent as non-splenectomized SCI controls. Overall, our findings show that functional T and B lymphocytes have minimal influence or dispensable contributions to NHO development after experimental SCI in mice.