Targeting Recipient Dendritic Cells with Sialic Acid-Modified Donor Alloantigen Prolongs Skin Transplant Survival

TL;DR

Modifying donor antigens with sialic acid and targeting them to recipient dendritic cells can prolong skin transplant survival by inducing immune tolerance.

Contribution

A novel method of targeting sialylated donor alloantigens to dendritic cell Siglecs to induce transplant tolerance is introduced.

Findings

Injecting α2,3 Sia-Kd into recipient mice prolonged skin graft survival.

This treatment increased CD4+CD62L+Foxp3+ regulatory T cells in recipients.

Siglec targeting on DC subsets is a promising strategy for transplant tolerance.

Abstract

Mature dendritic cells (DCs) are known to activate effector immune responses, whereas steady state immature DCs can induce tolerance. Several studies have targeted immature murine quiescent DCs in vivo with antigen, including donor alloantigens, for the induction of tolerance. Receptors expressed by specific DC subsets have been also targeted with antibodies linked with antigens to induce tolerance; for instance, in vivo targeting of the DCIR2+ DC subset with donor alloantigen resulted in long-term survival of heart and skin transplants. DCs also express sialic acid immunoglobulin-like lectin (Siglec) receptors, and these have been successfully targeted with myelin oligiodendrocyte glycoprotein (MOG) antigen to induce tolerance in experimental autoimmune encephalomyelitis (EAE). We investigated, in a mismatched model of skin transplant (B6Kd into B6 recipient mice), whether targeting a sialylated alloantigen Kd (Sia-Kd) to Siglecs on recipient DCs promoted transplant survival. The injection of α2,3 Sia-Kd into B6 recipient mice prior to B6Kd skin transplantation, by binding to Batf3 dependent DCs, resulted in prolonged skin graft survival and an increase in CD4+CD62L+Foxp3+ Tregs. Targeting Siglecs on DC subsets in vivo represents a novel way of improving transplant survival.

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