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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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A Data-Driven Approach to Quantifying Immune States in Sepsis
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Targeting Immune Cell Checkpoints during Sepsis.

Naeem K Patil1, Yin Guo2, Liming Luan3

  • 1Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. naeem.patil@vanderbilt.edu.

International Journal of Molecular Sciences
|November 15, 2017
PubMed
Summary
This summary is machine-generated.

Sepsis causes immune suppression, impairing infection control and increasing mortality. Blocking immune checkpoints like PD-1 can restore immune function and improve survival in sepsis patients.

Keywords:
2B4BTLACTLA-4LAG-3PD-1PD-L1T cell exhaustionTIM-3immunosuppressionimmunotherapymyeloid cellssepsis

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Sepsis is associated with increased morbidity and mortality, partly due to immunosuppression.
  • Dysfunction of both innate and adaptive immunity in sepsis hinders pathogen clearance and promotes secondary infections.

Purpose of the Study:

  • To investigate the role of inhibitory immune checkpoint molecules in sepsis-induced immunosuppression.
  • To evaluate the therapeutic potential of immune checkpoint inhibitors in sepsis.

Main Methods:

  • Review of pre-clinical and clinical studies on immune checkpoint molecule expression and function in sepsis.
  • Analysis of data on the effects of blocking immune checkpoints (PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, 2B4) in sepsis models.

Main Results:

  • Inhibitory immune checkpoint molecules are upregulated during sepsis, suppressing innate and adaptive immune cell functions.
  • Blocking these checkpoints in pre-clinical sepsis models enhances immune cell function, pathogen clearance, and host survival.

Conclusions:

  • Immune checkpoint blockade demonstrates significant potential as a therapeutic strategy for sepsis.
  • Further investigation into immunotherapy for sepsis is warranted.