Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells known to play a role in perpetuating a wide range of pathologies, such as chronic infections, autoimmune diseases, and cancer. MDSCs were first identified in mice by the markers CD11b+Gr1+, and later, based on their morphology, they were classified into two subsets: polymorphonuclear MDSCs, identified by the markers CD11b+Ly6G+Ly6CLow, and monocytic MDSCs, detected as being CD11b+Ly6G–Ly6CHi. MDSCs are studied as immunosuppressive cells in various diseases characterized by chronic inflammation and are associated with disease causes/triggers such as pathogens, autoantigens, and cancer. Therefore, different diseases may diversely affect MDSC metabolism, migration, and differentiation, thus influencing the generated MDSC functional features and ensuing suppressive environment. In order to study MDSCs in a pathology-free environment, we established and calibrated a highly reproducible mouse model that results in the development of chronic inflammation, which is the major cause of MDSC accumulation and immune suppression. The model presented can be used to study MDSC phenotypes, functional diversity, and plasticity. It also permits study of MDSC migration from the bone marrow to peripheral lymphatic and non-lymphatic organs and MDSC crosstalk with extrinsic factors, both in vivo and ex vivo. Furthermore, this model can serve as a platform to assess the effects of anti-MDSC modalities.
Bibliographical noteFunding Information:
The authors gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center and the Harold B. Abramson Chair in Immunology. The authors are also thankful for the grant support of the Israel Science Foundation (ISF), the Israeli Ministry of Health, the Israel Cancer Research Fund (ICRF), the Israel Ministry of Science and Technology, the Gross Foundation, the Bruce and Baila Waldholtz funds, and the Joseph and Matilda Melnick Funds as well as to Ms. Andrea Safir for generously providing editing expertise.
© 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.
- chronic inflammation
- immune suppression
- myeloid cells