Inhibition of S-adenosyl-L-homocysteine hydrolase alleviates alloimmune response by down-regulating CD4⁺ T-cell activation in a mouse heart transplantation model.

ABSTRACT:

Background

Transmethylation reactions play an important role on lymphocyte activation and function. S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitors prevent the feedback of transmethylation reactions by S-adenosyl-L-homocysteine (SAH) accumulation, a competitive antagonist of S-adenosylmethionine (SAM)-dependent methyltransferases. However, the role of SAH in solid organ transplantation is currently unclear.

Methods

A murine model of cardiac transplantation (BALB/C to C57B/6) was established to assess allograft survival, histology, and T cell infiltration. The reversible SAHH inhibitor, DZ2002, and irreversible SAHH inhibitor, adenosine dialdehyde (AdOx), were used to assess their immunosuppressive effects in murine cardiac transplantation, compared with mice with DMSO.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC7791210 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature