Different Effects of Tacrolimus on Innate and Adaptive Immune Cells in the Allograft Transplantation

Abstract

While tacrolimus (FK506) is currently used as immunosuppression therapy in transplant recipient, the immunological mechanism remains unknown. Herein, the immunoregulatory effects of FK506 were investigated in the physiological status and allogeneic skin transplantation. FK506 cannot significantly alter the functions of innate immune cells (macrophages and neutrophils) and adaptive immune cells (T cells) in the physiological status. However, it can effectively delay allogeneic skin-graft rejection through ameliorating the T cell responses, but not myeloid-derived innate immune cell responses. Importantly, it did not affect the allograft recipient macrophage innate immune defence capacity to bacteria. In clinics, FK506 treatment can significantly control the cytokine production in T cells, but not non-T cells. This study shows targeting calcineurin signalling, FK506, to be essential in inducing allograft tolerance, but not to damage the innate defence capacity, validating the immune cell phenotypes as a potential marker in transplantation following FK506 treatment.

Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System

“…The main finding in our study is the observation that cells from EAE + Art mice presented lower expression of chemokine receptors, reduced migratory ability, and did not leave the secondary lymphoid organs in the course of EAE. Similar results are found in mice and transplanted/MS patients treated with FTY720 (fingolimod) and FK506 (tacrolimus) [46][47][48][49][50][51]. In our study, we found that T cells maintained their encephalitogenic potential after Art treatment, as transfer of cells from EAE + Art mice to RAG2 À/À mice resulted in normal disease development.…”

Induction of liver transplant immune tolerance in an outbred rat strain model using tacrolimus Subtitle: Therapeutic effect of tacrolimus in rat orthotopic liver transplantation models

“…We found that FK506 treatment signi cantly prolonged graft survival and reduced hepatic in ammation. In addition, FK506 suppressed pro-in ammatory T helper (Th)1/Th17 responses [19,20] and Foxp3 + Treg [21]. However, FK506 also inhibits immunomodulatory IL-10 cytokines [22].…”

Topical Delivery of Immunosuppression to Prolong Xenogeneic and Allogeneic Split-Thickness Skin Graft Survival

“…Potential drugs include those that inhibit T cell targets, which are considered important in the rejection of skin. 41 We will also study the effect of these topical, slow release immunosuppressant-loaded products on the immunological reaction to and survival of allogenically transplanted primarily vascularized skin flaps.…”