Interleukin-17 promotes early allograft inflammation.

Area of Science:

• Immunology
• Transplantation Biology

Background:

• Acute cellular rejection is mediated by T cells, often producing interferon-gamma.
• Interferon-gamma is not essential for graft destruction, prompting investigation into other inflammatory mediators.
• Interleukin-17A (IL-17) role in intragraft inflammation requires further elucidation.

Purpose of the Study:

• To evaluate the contribution of IL-17 to intragraft inflammation in major histocompatibility complex-mismatched heart transplants.
• To understand the impact of IL-17 on immune cell recruitment and allograft rejection kinetics.

Main Methods:

• Utilized a mouse model of cardiac allotransplantation (A/J into BALB/c).
• Compared wild-type recipients with IL-17(-/-) knockout recipients.
• Assessed chemokine production, immune cell infiltration (neutrophils, T cells), T cell priming, and allograft rejection timelines.
• Investigated the role of CD8 T cells in IL-17-deficient recipients.

Main Results:

• Intragraft IL-17 production was detected early after transplantation (day 2).
• IL-17 deficiency led to reduced CXCL1/CXCL2 chemokine production and delayed neutrophil/T cell recruitment.
• Despite early differences, overall cellular infiltration was comparable by day 7.
• T cell priming was unaffected by IL-17 absence; rejection kinetics were similar in wild-type and IL-17(-/-) mice.
• In CD8-depleted mice, IL-17 deficiency delayed allograft rejection.
• Effector T cell infiltration into allografts was impaired in IL-17(-/-) recipients.

Conclusions:

• Locally produced IL-17 amplifies early intragraft inflammation post-transplantation.
• IL-17 facilitates T cell recruitment, contributing to tissue injury.
• Targeting the IL-17 signaling pathway may reduce transplant-associated injury and enhance organ survival when combined with other therapies.