Heparin affects the induction of regulatory T cells independent of anticoagulant activity and suppresses the allogeneic immune responses.

Heparin affects the induction of regulatory T cells independent of anticoagulant activity and suppresses the allogeneic immune responses. Clin Exp Immunol. 2020 Jun 19;: Authors: Kashiwakura Y, Kojima H, Kanno Y, Hashiguchi M, Kobata T Abstract Heparin is a widely used anticoagulant that enhances antithrombin (AT) activity. However, heparin also suppresses immune and inflammatory responses in various rodent models and clinical trials, respectively. The mechanism by which heparin suppresses immune responses is unclear. The effect of heparin on regulatory T cells (Tregs) in allogeneic immune responses was analysed using an acute graft-versus-host disease (aGVHD) mouse model and mixed lymphocyte reactions (MLRs). In vitro culture systems were utilized to study the effects of heparin on Tregs. Heparin administration reduced mortality rates and increased the proportion of Tregs in the early post-transplantation period of aGVHD mice. In both murine and human MLRs, heparin increased Tregs and inhibited responder T cell proliferation. Heparin promoted functional CD4+ CD25+ Foxp3+ Treg generation from naïve CD4+ T cells, increased interleukin (IL)-2 production, and enhanced the activation of pre-existing Tregs with IL-2. Heparin-induced Treg increases were not associated with anticoagulant activity through AT but required negatively charged sulphation of heparin. Importantly, N-acetyl heparin, a chemically modified heparin without anticoagul...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research