TIGIT regulates CD4⁺ T cell immunity against polymicrobial sepsis

Area of Science:

• Immunology
• Critical Care Medicine
• Pathophysiology

Background:

• Sepsis is a leading cause of mortality and a significant healthcare burden in intensive care units.
• Immune checkpoints, such as T cell immunoglobulin and ITIM domain (TIGIT), are critical regulators of T cell responses.
• The role of TIGIT in the early stages of sepsis remains largely unexplored.

Purpose of the Study:

• To investigate the function of the negative immune checkpoint TIGIT in the early phase of experimental sepsis.
• To evaluate the therapeutic potential of targeting TIGIT in sepsis management.

Main Methods:

• A murine model of sepsis was established using cecal ligation and puncture (CLP).
• TIGIT and CD155 expression was analyzed in splenocytes and sepsis-involved organs via flow cytometry, qPCR, and immunofluorescence.
• Phenotypic analysis of TIGIT-deficient mice and wild-type mice treated with anti-TIGIT antibody assessed immune cell function, clinical severity, and bacterial burden.

Main Results:

• TIGIT expression was significantly upregulated in splenic T cells and NK cells at 24 hours post-CLP.
• TIGIT deficiency or blockade enhanced CD4+ T cell proliferation and cytokine production, alongside improved innate immune cell effector function.
• Mice lacking TIGIT or treated with anti-TIGIT antibody exhibited reduced tissue injury and bacterial load in a sepsis model.

Conclusions:

• TIGIT significantly modulates CD4+ T cell responses during polymicrobial sepsis.
• Targeting TIGIT demonstrates a promising therapeutic strategy for managing sepsis.