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New insights into the functions of MDSCs in autoimmune pathogenesis

Cellular & Molecular Immunology volume 20, pages 548–550 (2023)Cite this article

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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive effects that are expanded under pathological conditions. In the past decade, MDSCs have generated significant research interest and increased attention. Recently, clinical observations and animal model studies have shown that MDSCs accumulate during the development of various autoimmune diseases, including primary Sjögren’s syndrome (pSS). pSS is a common systemic autoimmune disease characterized by lymphocyte infiltration and tissue inflammation in the salivary glands (SG) and lacrimal glands, resulting in dry mouth and dry eyes. Here, we review the latest evidence and provide new insights into the roles of MDSCs in the pathogenesis of autoimmune diseases, focusing on the functional changes in MDSCs and their therapeutic potential in autoimmune diseases.

Extensive studies have characterized the roles of MDSCs in the development of autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), type I diabetes, systemic lupus erythematosus (SLE) and autoimmune uveoretinitis. Although the expansion of MDSCs has been observed in various autoimmune diseases, evidence suggests the diverse functions of MDSCs in different autoimmune diseases. Early studies showed that MDSCs could inhibit inflammatory reactions by inducing T-cell apoptosis in mice with experimental autoimmune encephalomyelitis (EAE) [1]. Moreover, adoptive transfer of MDSCs from EAE mice significantly suppressed the progression of EAE by inhibiting Th1 and Th17 immune responses [2]. However, Yi et al. found that M-MDSCs promoted the differentiation of Th17 cells in EAE mice, whereas the depletion of MDSCs markedly reduced the Th17 response and attenuated the severity of EAE in mice [3]. In addition, proinflammatory and regulatory effects of MDSCs were observed in the development of autoimmune arthritis. Fujii et al. identified a protective role of G-MDSCs in mice with collagen-induced arthritis (CIA), while M-MDSCs could promote Th17 cell polarization and exacerbate disease progression in CIA mice [4, 5]. In lupus-prone mice, MDSCs were found adjacent to spleen B-cell follicles and could alleviate the development of lupus-like disease by inhibiting B-cell responses [6]. Interestingly, MDSCs have been shown to induce the expansion of regulatory B cells through iNOS production and ameliorate the development of SLE [6]. Notably, a recent clinical investigation showed that MDSCs derived from SLE patients promoted Th17 cell differentiation in an Arg-1-dependent manner, leading to the exacerbation of disease progression, indicating the diverse functions of MDSCs during SLE development [7].

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 82271854, 81971542, 82171771, 91842304, and 82071817), the Shenzhen Science and Technology Program (JCYJ20210324114602008), the Hong Kong Research Grants Council Theme-Based Research Scheme (T12-703/19 R) and the Centre for Oncology and Immunology under the Health@InnoHK Initiative by the Innovation and Technology Commission, Hong Kong, China.

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  1. These authors contributed equally: Ke Rui, Na Peng.

Authors and Affiliations

  1. Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China

    Ke Rui

  2. Department of Rheumatology, the Second People’s Hospital, China Three Gorges University, Yichang, China

    Na Peng

  3. Department of Pathology and HKU-Shenzhen Hospital, The University of Hong Kong, Hong Kong, China

    Fan Xiao & Liwei Lu

  4. Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China

    Fan Xiao & Liwei Lu

  5. Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China

    Jie Tian

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  1. Ke Rui
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Correspondence to Liwei Lu or Jie Tian.

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Rui, K., Peng, N., Xiao, F. et al. New insights into the functions of MDSCs in autoimmune pathogenesis. Cell Mol Immunol 20, 548–550 (2023). https://doi.org/10.1038/s41423-023-01004-1

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