Myeloid-Derived Suppressor Cells

**109**

**Chapter 7**

**Abstract**

(MDSCs)

KLF4-Mediated Plasticity of

*Daping Fan, Samir Raychoudhury and Walden Ai*

and the underlying mechanisms are discussed.

cancer, wound healing

pathological wound healing [9–11].

immature cells possess typical CD11b+

**1. Introduction**

Myeloid-Derived Suppressor Cells

Robustness of tissues refers to their capability to maintain normal functions despite perturbation such as injuries. Recent studies suggest a key role of the

immune system in injury repair. In this process, several immune cell lineages exhibit considerable plasticity as they migrate toward the site of damage and contribute to repair. For example, myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells and possess phenotypic plasticity in cancer, a pathological status that is considered as "wounds that do not heal." They are characterized by their potent ability to suppress immune responses. In cutaneous wound healing, MDSCs not only execute their immunosuppressive function to inhibit inflammation but also stimulate cell proliferation once they adopt a fate of a totally different cell type. At a molecular level, we found that Krüppel-like factor 4 (KLF4), a transcription factor with multiple roles in homeostasis and disease development plays a critical role in regulating MDSCs. In this review, KLF4-mediated plasticity of MDSCs

**Keywords:** KLF4, FSP-1, myeloid-derived suppressor cells (MDSCs), plasticity,

KLF4 is a member of the Krüppel-like factor family, a group of zinc fingercontaining transcription factors that are highly homologous with the Drosophila Krüppel protein [1–4]. It has important functions in a variety of cellular processes that include cell proliferation, differentiation, development, and maintenance of normal tissue homeostasis [5]. KLF4 has also been shown to act either as a tumor suppressor or an oncoprotein in a context-dependent manner [6–8]. Moreover, KLF4 is critical to barrier function of the skin and promotes physiological and

MDSCs are bone marrow-derived cells present in bone marrow, spleen, and circulation. They are a heterogeneous collection of immature myeloid cells. These

Ly6G+

markers in humans. The main function of MDSCs is their potent ability to suppress the host immune responses, especially T-cell proliferation and cytokine production [12]. They possess phenotypic plasticity in cancer [13, 14], a pathological status that is considered as "wounds that do not heal." However, while the involvement of MDSCs in wound healing has been shown by their recruitment to the wound sites [15], the

markers in mice with a wider range of
