Systemic T Cell Exhaustion Dynamics Is Linked to Early High Mobility Group Box Protein 1 (HMGB1) Driven...

Area of Science:

• Immunology
• Trauma Research
• Molecular Biology

Background:

• High mobility group box protein 1 (HMGB1) surges early after polytrauma (PT).
• HMGB1's role in PT-induced immune dysregulation and its effect on RAGE and TLR4 is unclear.
• Understanding HMGB1's impact on immune cell receptors is crucial for trauma management.

Purpose of the Study:

• To investigate HMGB1's role in mediating immune responses post-PT.
• To assess HMGB1's influence on receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4) expression on immune cells.
• To evaluate the therapeutic potential of HMGB1 neutralization in PT.

Main Methods:

• Utilized a polytrauma (PT) rat model.
• Administered anti-HMGB1 polyclonal antibody for HMGB1 neutralization.
• Assessed circulating inflammatory cytokines, monocyte/macrophage and T cell dynamics.
• Measured cell surface expression of RAGE and TLR4 on immune cells at 1, 3, and 7 days post-trauma (dpt).

Main Results:

• PT induced hyper-inflammatory responses with increased monocytes/macrophages and decreased T cells.
• RAGE and TLR4 expression was elevated on monocytes/macrophages but diminished on T cells (CD4+, CD8+) in PT rats.
• HMGB1 neutralization restored T cell counts and normalized RAGE/TLR4 expression on T cells.
• γδ TCR T cells were not significantly affected by HMGB1 neutralization.

Conclusions:

• Early HMGB1 surge in PT contributes to T cell exhaustion and dysfunction.
• HMGB1 neutralization ameliorates immune dysregulation by restoring T cell receptor expression.
• Targeting HMGB1 may be a viable strategy to improve immune function after polytrauma.