Traumatic Brain Injury Alters Dendritic Cell Differentiation and Distribution in Lymphoid and Non-Lymphoid Organs

Abstract: Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary injury remain incompletely understood. In particular, the impact of TBI on the differentiation and maintenance of dendritic cells (DCs), remains completely unknown. Here, we report that DC- differentiation, maintenance and functions are altered at both early and late phases of TBI. Our studies identify that; 1. frequencies and absolute numbers of DCs in the spleen and BM are altered at both acute and late phases of TBI; 2. surface expression of key molecules involved in antigen presentation of DCs were affected both at early and late phases of TBI; 3. distribution and functions of tissue-specific DC subsets of both circulatory and lymphatic systems were imbalanced following TBI; 4. early differentiation program of DCs, especially the commitment of hematopoietic stem cells to common DC progenitors, were deregulated after TBI; and 5. intracellular ROS levels were reduced in DC progenitors and differentiated DCs at both early and late phases of TBI. Our data demonstrate, for the first time, that TBI affects the distribution pattern of DCs and induces an imbalance among DC subsets in both lymphoid and non-lymphoid organs. In addition, the current study demonstrates that TBI results in reduced levels of ROS in DCs at both early and late phases of TBI, which may explain altered DC differentiation paradigm following TBI. A deeper understanding on the molecular mechanisms that contribute to DC defects following TBI would be essential and beneficial in treating infections in patients with acute central nervous system (CNS) injuries.