Regulatory Myeloid Cells in Transplantation

Abstract

Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin.

Carbon monoxide impairs mitochondria‐dependent endosomal maturation and antigen presentation in dendritic cells

“…Intraluminal antigens exit from the ERgosome being degraded by the proteasome and reinternalized by the transporter associated with antigen processing (TAP) (8). MHCs-containing vesicles fuse with the ERgosome in a LPS/IKK2/glycolysis-dependent manner (9). Finally, as ERgosomes do not require to be transported to the perinuclear zone, pMHCs are directly presented in the surface of DCs (10).…”

“…A tight regulation of these processes defines whether these cells promote either Correspondence: Dr. Alexis M. Kalergis and Dr. Susan Bueno e-mail: akalergis@bio.puc.cl; akalergis@icloud.com; sbueno@bio.puc.cl immunity or tolerance [1,[8][9][10][11][12]. Due to these features of DCs, in the last years significant efforts have been made to define the molecular and cellular elements that modulate their function [13].…”

“…Thus, modulation of DCs is considered as a promising therapeutic strategy to either treat or prevent inflammatory/autoimmune diseases [17]. Among several regulatory molecules that have been characterized in DCs [9,[16][17][18][19], one is the anti-stress and Heme-degrading enzyme Heme-oxygenase 1 (HO-1) [18]. Heme degradation by HO-1 releases free iron (Fe +2 ), biliverdin, and carbon monoxide (CO) [18].…”

Sphingosine 1-Phosphate Receptor 3–Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion Injury

“…33 Additionally, current therapies for allograft rejection, cancer, or autoimmune diseases use nonspecific immunosuppressive drugs that are associated with adverse side effects and limited because of lack of antigen-specific tolerance. Cell-based therapy using regulatory immune cells (T REG s, 34 myeloid cells, 35 or DCs 36,37 ) is a strategy that induces potential antigen-specific tolerance. Pharmacologic or biologic strategies induce regulatory or tolerogenic DCs, 38 which are immature, maturationresistant, or alternatively activated cells that express low levels of MHC and costimulatory molecules.…”

Proceedings: Immune Tolerance and Stem Cell Transplantation: A CIRM Mini-Symposium and Workshop Report

“…Antibody-based Alemtuzumab Mature lymphocyte depletion [5] Abatacept Costimulation blockade [6] Cell-based Regulatory T cells Downregulation of detrimental molecular pathways [9] Tolerogenic dendritic cells [10] Myeloid-derived suppressor cells [11,12] Mesenchymal stromal cells [13] Natural killer T cells [14] Talib, Millan, Jorgenson et al…”