Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppression and tolerance, they will be further referred to as myeloid regulatory cells (MRCs). In recent years, MRCs have emerged as a therapeutic target or have been regarded as a potential cellular therapeutic product for tolerance induction. However, several open questions must be addressed to enable the therapeutic application of MRCs including: how do they function at the site of inflammation, how to best target these cells to modulate their activities, and how to isolate or to generate pure populations for adoptive cell therapies. In this review, we will give an overview of the current knowledge on MRCs in inflammation, autoimmunity, and transplantation. We will discuss current strategies to target MRCs and to exploit their tolerogenic potential as a cell-based therapy.

Centre de Recherche en Transplantation et Immunologie UMR1064 INSERM Université de Nantes Nantes France

Centro Nacional de Microbiologia Instituto de Salud Carlos 3 Majadahonda 28220 Madrid Spain

Department of Biological Sciences Faculty of Science and Engineering University of Limerick Limerick Ireland

Department of Immunology Faculty of Medicine Uludag University Bursa Turkey

Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow Poland

Institut de Transplantation Urologie Nephrologie CHU Nantes Nantes France

Institute of Biophysics The Czech Academy of Sciences Brno Czech Republic

Institute of Immunology University of Münster Münster Germany

Molecular and Translational Cardiology Department of Cardiovascular Medicine University Hospital Münster Münster Germany

San Raffaele Telethon Institute for Gene Therapy San Raffaele Scientific Institute IRCCS Via Olgettina 58 20132 Milan Italy

Translational Research in Gastrointestinal Disorders Department of Chronic Diseases Metabolism and Ageing KU Leuven Leuven Belgium

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