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Siglec-E is a Critical Inhibitory Receptor Controlling APC Activation and T Cell-Mediated Transplant Rejection

ABSTRACT: Early after transplantation, inflammation and tissue injury release danger signals that activate myeloid innate immune cells like DCs, driving adaptive immune responses and acute rejection. Current immunosuppressive drugs primarily target T cells, leaving innate immunity inadequately controlled. Siglec-E (SigE), an innate inhibitory receptor, binds sialic acid-carrying ligands to suppress inflammatory responses. In mouse heart transplants, SigE is upregulated in graft-infiltrating myeloid cells, including DCs. Human homologs Sig-7 and Sig-9 are also upregulated in rejecting heart and kidney transplant biopsies. Genetic ablation of SigE in recipients accelerates acute rejection of heart, kidney, and skin allografts. SigE-deficient DCs are more susceptible to activation by danger signals and show enhanced NF-kB activation and TNF-a production, increasing alloreactive T-cell responses. Overexpressing SigE on DCs reduces their activation by DAMPs and their T-cell allostimulatory capacity. Thus, SigE is a crucial inhibitory receptor controlling APC activation and T cell-mediated transplant rejection.

ORGANISM(S): Mus musculus

PROVIDER: GSE271770 | GEO | 2025/03/25

REPOSITORIES: GEO

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