The mucosal immune system plays a vital role in protecting the host from the external environment. Its major challenge is to balance immune responses against harmful and harmless agents and serve as a ‘homeostatic gate keeper’. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of undifferentiated cells that are characterized by an immunoregulatory and immunosuppressive phenotype. Herein we postulate that MDSCs may be involved in shaping immune responses related to mucosal immunity, due to their immunomodulatory and tissue remodeling functions. Until recently, MDSCs were investigated mainly in cancerous diseases, where they induce and contribute to an immunosuppressive and inflammatory environment that favors tumor development. However, it is now becoming clear that MDSCs participate in non-cancerous conditions such as chronic infections, autoimmune diseases, pregnancy, aging processes and immune tolerance to commensal microbiota at mucosal sites. Since MDSCs are found in the periphery only in small numbers under normal conditions, their role is highlighted during pathologies characterized by acute or chronic inflammation, when they accumulate and become activated. In this review, we describe several aspects of the current knowledge characterizing MDSCs and their involvement in the regulation of the mucosal epithelial barrier, their crosstalk with commensal microbiota and pathogenic microorganisms, and their complex interactions with a variety of surrounding regulatory and effector immune cells. Finally, we discuss the beneficial and harmful outcomes of the MDSC regulatory functions in diseases affecting mucosal tissues. We wish to illuminate the pivotal role of MDSCs in mucosal immunity, the limitations in our understanding of all the players and the intricate challenges stemming from the complex interactions of MDSCs with their environment.
Bibliographical noteFunding Information:
The authors acknowledge Nira Twaik-Nakav, Kerem Ben-Meir, Or Reuven, Leonor Daniel, Yaron Meirow and Chaim Preiser for reading the review and providing their valuable input. The authors gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center and the Harold B. Abramson Chair in Immunology. They also thank the grant support by 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.
© 2021 Elsevier Inc.
- Cell damage
- Chronic inflammation
- Epithelial barrier
- Mucosal immunity
- Myeloid derived suppressor cells