IL-17 promotes Type 1 T cell response through modulating dendritic cell function in acute allograft rejection

Area of Science:

• Immunology
• Transplantation Biology
• Cytokine Signaling

Background:

• Interleukin-17 (IL-17) is implicated in various disease pathologies.
• The specific role and source of IL-17 in allograft rejection remain incompletely understood.
• Early events in allograft rejection, including dendritic cell (DC) maturation, are critical for immune response initiation.

Purpose of the Study:

• To investigate the source and mechanism of IL-17 during cardiac allograft rejection.
• To determine the impact of IL-17 on dendritic cell function and immune response in transplantation.
• To evaluate the therapeutic potential of modulating IL-17 activity in allograft rejection.

Main Methods:

• Quantification of IL-17 expression during early stages of cardiac allograft rejection.
• Identification of IL-17 producing cells using flow cytometry (CD3+, CD11c+, CD11b+, NK1.1+).
• In vivo blockade of IL-17 activity and assessment of DC maturation, cytokine profiles, and Th1 response.
• Adoptive transfer of IL-17-treated dendritic cells (DCs) and evaluation of allograft survival and T cell responses.
• In vitro experiments using recombinant IL-17 to assess its effect on bone marrow-derived dendritic cells (BMDCs) and T cell function.

Main Results:

• IL-17 expression peaked early in cardiac allograft rejection, preceding DC maturation.
• CD3+ T cells were identified as the primary source of IL-17; other immune cells expressed minimal IL-17.
• IL-17 blockade suppressed DC maturation, reduced inflammatory cytokines, and impaired Th1 responses.
• Adoptive transfer of IL-17-treated DCs led to prolonged allograft survival and reduced IFN-γ production.
• Recombinant IL-17 upregulated co-stimulatory molecules on BMDCs and enhanced their capacity to stimulate T cells.

Conclusions:

• Early elevated levels of IL-17 significantly contribute to allograft rejection.
• IL-17 modulates dendritic cell function, thereby influencing the adaptive immune response.
• Targeting IL-17 presents a potential therapeutic strategy to mitigate allograft rejection.