Role of myeloid-derived suppressor cells in autoimmune disease

Abstract

Myeloid-derived suppressor cells (MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-based cell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy.

GM-CSF: An immune modulatory cytokine that can suppress autoimmunity

“…MDSCs have been shown to regulate immune responses during autoimmune conditions (181, 182). It has been suggested that MDSCs suppress T cell activity through the secretion of inducible nitric oxide synthase (iNOS) and arginase-1 (182).…”

“…MDSCs have been shown to regulate immune responses during autoimmune conditions (181, 182). It has been suggested that MDSCs suppress T cell activity through the secretion of inducible nitric oxide synthase (iNOS) and arginase-1 (182). GM-CSF has been shown to not only promote the development of MDSCs from bone marrow precursors (183) but also determine their suppressive capacities (184).…”

The Changing Landscape of Renal Inflammation

“…Their trafficking is mainly dictated by the chemokine receptor CCR2. [84, 85] They are found in mouse models of rheumatoid arthritis, diabetes and multiple sclerosis (EAE). Peripheral blood naïve monocytes (CD11b +, Ly6G − ) also display in vitro intrinsic suppressive properties by inhibiting T cell proliferation through a mechanism that requires cell-contact and partially, nitric oxide (NO) production.…”

Activated Circulating Myeloid-Derived Suppressor Cells in Patients with Dilated Cardiomyopathy

“…We and others have demonstrated that CD14 + HLA-DR -/low cells share multiple characteristics with MDSCs [15] and expand under a variety of pathological conditions, such as cancer [16][17][18][19], inflammation [20,21], and autoimmune diseases [22,23]. Presently, the inhibitory properties of MDSCs are thought to be mediated by a number of different mechanisms, including arginase-1 (Arg-1), inducible nitric oxidase (iNOS), transforming growth factor-beta (TGF-β), and interleukin-10 (IL-10) as well as the induction of regulatory T cells [10,23].…”