Liver-derived IL-10 as a potential inhibitor of a TH1-deviating crosstalk between donor DC and recipient NK cells during combined liver-kidney transplantation

• During transplantation DCs within the allograft become activated and migrate to secondary lymphoid organs (SLO) where they activate NK cells and alloreactive T cell. Previous findings suggest that a liver graft is less prone to induce rejection compared to a renal graft but the mechanisms are still unclear. We compared changes in graft gene expression of inflammatory mediators known to participate in transplantation-induced DC activation in the liver and kidney in patients undergoing combined liver-kidney transplantation (n=8). Real-time PCR analysis revealed a similar up-regulation of mRNA for the DC-activation-associated inflammatory mediators TNF-α, IL-1β and IFN-gamma after reperfusion in the liver and kidney. While no reperfusion-dependent mRNA increase for IL-10 was found in transplated grafts, serial measurement of cytokine levels in peripheral blood revealed that IL-10 levels increased 60-fold in serum shortly (within 1 h) after liver, but before kidney, reperfusion and returned to pre-transplant levels at day 2 post-transplantation (n=3). No significant changes were seen in IL-12 levels. DCs matured with a cocktail consisting of IFN-γ, TNF-α and IL-1β demonstrated a strong and sustained production of CXCR3-ligands which are indispensable for DC-mediated recruitment of blood NK cells into SLO and their subsequent boosting of TH1-deviated alloresponses. Addition of IL-10 during DC maturation significantly decreased the production of all three CXCR3-ligands (CXCL9, CXCL10 and CXCL11). These findings indicate that IL-10 is selectively and rapidly released during liver transplantation, probably due to accumulation during the ischehmia period. This release may potentially inhibit a TH1-deviating crosstalk between donor DC and recipient NK cells.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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