The mobilisation of early mature CD56dim-CD16bright NK cells is blunted following a single bout of vigorous intensity exercise in Type 1 Diabetes

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that targets and destroys insulin-secreting pancreatic beta cells. Although T cell mediated, a number of other immune cells are also critically involved in coordinating the events leading to T1D. Specifically, innate subsets play an important role in the pathogenesis of T1D. NK cells are one of the first cell types to infiltrate the pancreas, causing damage and release of beta cell antigens. Previous work in our group has shown differential mobilisation of highly differentiated CD8+ T cells during vigorous intensity exercise in T1D compared to a control cohort. Here, we aimed to explore exercise-induced mobilisation of other cell types involved in T1D pathogenesis. In this study, we investigated the effects of a single bout of vigorous (80% predicted VO2max) intensity exercise on innate cell mobilisation in T1D and control participants. T1D (N=12, mean age 33.2yrs, predicted VO₂max 32.2 ml.kg.min⁻¹, BMI 25.3 kg.m⁻²) and control (N=12, mean age 29.4yrs, predicted VO2 max 38.5 ml.kg.min⁻¹, BMI 23.7 kg.m⁻² male participants completed a 30-minute bout of cycling at 80% predicted VO₂ max in a fasted state. Peripheral blood was collected at baseline, immediately post-exercise, and 1 hour post-exercise. NK cell subsets mobilised during vigorous intensity exercise in both control and T1D participants. However, mature NK cells, defined as the CD56dimCD16bright subset, displayed a lower percentage increase following vigorous intensity exercise in T1D participants (Control: 185.12%, T1D: 97.06%). This blunted mobilisation was specific to early mature NK cells (KIR+) but not later differentiated NK cells (KIR+CD57+). Myeloid lineage subsets mobilised to a similar extent in both control and T1D participants. In conclusion, vigorous exercise mobilises innate immune cells in people with T1D albeit to a different extent to those without T1D. This mobilisation of innate immune cells provides a mechanistic argument to support exercise in people with T1D where it has the potential to improve surveillance for infection and to modulate the autoimmune response to the beta cell.