Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies

Abstract

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn’s disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.

Multi-omics provide evidence for an anti-inflammatory immune signature and metabolic alterations in patients with Long COVID Syndrome – an exploratory study

“…However, the pro-inflammatory M1 state may be switched, e.g. by oxidized phospholipids accumulated during acute infection, to a tolerogenic M2-like phenotype ( 44, 45 ), thus becoming long-lived cells coordinating tissue regeneration ( 46 ). Lipid peroxidation may occur consequent to inflammatory responses also during sterile inflammation such as atherosclerosis ( 47 ) and thus represents a plausible mechanism inducing tolerogenic macrophage polarization after SARS-CoV-2 infection.…”

Retinoic Acid-Containing Liposomes for the Induction of Antigen-Specific Regulatory T Cells as a Treatment for Autoimmune Diseases

“…The restoration of antigen-specific tolerance is essential for the development of a curative therapy for autoimmune diseases. TolDCs have shown promising results in the induction of antigen-specific tolerance in animal models and positive results in clinical trials [22]. Here, we focused on the naturally occurring tolerance-inducing compound RA and evaluated several methods for delivering RA to dendritic cells in vitro and in vivo.…”

“…This tolerance-inducing ability makes tolDCs interesting targets for the development of antigenspecific immunotherapy for autoimmune and chronic inflammatory diseases. Ex vivo culturing of patient DCs, converting them to tolDCs that present a disease-specific antigen and reinjecting them into the patient has already shown to be promising in clinical trials for several autoimmune diseases [22]. However, the process of isolating DC precursors from patients, stimulating the cells ex vivo and injecting them back into patients will remain not only labor intensive, but is also restricted to highly specialized cell culture facilities, thereby limiting the number of patients to be treated.…”

Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3

“…The expression of α‐SMA and collagen‐1A1 in fibroblasts was significantly increased with M2a CM stimulation while compared with that in other groups. When it comes to TGF‐β1, which is critical to induce PF and promote the ECM production, 54 CM from M2a, M2b and M2c could all elevate the expression level after incubation, suggesting the comprehensive roles of the three subtypes of M2 macrophages in the fibrosis induction.…”