Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients

Whitfield-Larry, Fatima; Felton, Jamie L.; Buse, John B.; Su, Maureen A.

doi:10.1016/j.clim.2014.04.006

Cited by 52 publications

(70 citation statements)

References 29 publications

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“…Mo‐MDSCs respond to their local environmental milieu, modulating their function in response to stimulation. This was demonstrated in one study illustrating the T‐cell suppressive function of Mo‐MDSCs obtained from patients with type I diabetes, which was significantly enhanced after in vitro stimulation with the cytokines interleukin (IL)‐1β and granulocyte macrophage‐colony stimulating factor (GM‐CSF) …”

Section: Introductionmentioning

confidence: 91%

“…More recently, it has been shown that MDSCs may have pathogenic implications in autoimmune responses . Interestingly, in contrast to the situation in tumors, MDSC function in autoimmune diseases may involve both immunosuppressive and proinflammatory functions . A recent study reported that Mo‐MDSCs within the peripheral blood of patients with psoriasis exert reduced T‐cell suppressive ability, compared to melanoma‐derived Mo‐MDSCs .…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] Interestingly, in contrast to the situation in tumors, MDSC function in autoimmune diseases may involve both immunosuppressive and proinflammatory functions. 9,[12][13][14] A recent study reported that Mo-MDSCs within the peripheral blood of patients with psoriasis exert reduced T-cell suppressive ability, compared to melanoma-derived Mo-MDSCs. 15 Similarly, Mo-MDSCs derived from patients with inflammatory bowel disease failed to suppress T cells, which was associated with downregulation of CCAAT/enhancerbinding protein beta (CEBP-b) expression.…”

Section: Introductionmentioning

confidence: 99%

“…This was demonstrated in one study illustrating the T-cell suppressive function of Mo-MDSCs obtained from patients with type I diabetes, which was significantly enhanced after in vitro stimulation with the cytokines interleukin (IL)-1b and granulocyte macrophage-colony stimulating factor (GM-CSF). 12 Findings from studies on experimental autoimmune encephalomyelitis (EAE) have reported an accumulation in the number of CD11b hi Ly6G + Ly6C À MDSCs within the spleen of mice prior to disease resolution, while a separate study demonstrated that CD11b + Gr-1 + MDSCs act as crucial effector cells, playing a role in demyelination and promotion of Th17 cell differentiation in active EAE. 10,16 At present, there are very few human studies on the role of MDSCs in MS. Ioannou et al…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

et al. 2018

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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system involving dysregulated encephalitogenic T cells. Myeloid-derived suppressor cells (MDSCs) have been recognized for their important function in regulating T-cell responses. Recent studies have indicated a role for MDSCs in autoimmune diseases, but their significance in MS is not clear. Here, we assessed the frequencies of CD14 HLA-DR monocytic MDSCs (Mo-MDSCs) and CD33 CD15 CD11b HLA-DR granulocytic MDSCs (Gr-MDSCs) and investigated phenotypic and functional differences of Mo-MDSCs at different clinical stages of MS and in healthy subjects (HC). Increased frequencies of Mo-MDSCs (P < 0.05) and Gr-MDSCs (P < 0.05) were observed in relapsing-remitting MS patients during relapse (RRMS-relapse) compared to stable RRMS (RRMS-rem). Secondary progressive MS (SPMS) patients displayed a decreased frequency of Mo-MDSCs and Gr-MDSCs compared to HC (P < 0.05). Mo-MDSCs within RRMS patients expressed significantly higher cell surface protein levels of CD86 and CD163 compared to SPMS patients. Mo-MDSCs within SPMS exhibited decreased mRNA expression of interleukin-10 and heme oxygenase 1 compared to RRMS and HC. Analysis of T-cell regulatory function of Mo-MDSCs demonstrated T-cell suppressive capacity in RRMS and HCs, while Mo-MDSCs of SPMS promoted autologous T-cell proliferation, which aligned with a differential cytokine profile compared to RRMS and HCs. This study is the first to show phenotypic and functional shifts of MDSCs between clinical stages of MS, suggesting a role for MDSCs as a therapeutic target to prevent MS disease progression.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

et al. 2018

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“…Successful treatment was accompanied by enhanced CpG uptake and expansion of CD19 + dendritic and myeloid-derived suppressor cell (MDSC)-like cells, leading to a reduction in cytokine responses. Notably, MDSCs accumulate in other chronic inflammatory diseases (such as arthritis, diabetes, and multiple sclerosis), but may be sub-optimally active [26], making them potential targets for treatment [27]. Interestingly, treatment of L. panamensis infected mice with NP-CpG did not lead to preferential development of a T helper type 1 (Th1)-like response.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model

et al. 2016

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Leishmania (Viannia) panamensis (L. (V.) panamensis) is a species of protozoan parasites that causes New World leishmaniasis, which is characterized by a hyper-inflammatory response. Current treatment strategies, mainly chemotherapeutic, are suboptimal due to adverse effects, long treatment regimens, and increasing drug resistance. Recently, immunotherapeutic approaches have shown promise in preclinical studies of leishmaniasis. As NPs may enable broad cellular immunomodulation through internalization in phagocytic and antigen-presenting cells, we tested the therapeutic efficacy of biodegradable NPs encapsulating a pathogen-associated molecular pattern (PAMP), CpG-rich oligonucleotide (CpG; NP-CpG), in mice infected with L. (V.) panamensis. NP-CpG treatment reduced lesion size and parasite burden, while neither free CpG nor empty NP showed therapeutic effects. NP-encapsulation led to CpG persistence at the site of infection along with an unexpected preferential cellular uptake by myeloid derived suppressor cells (MDSCs; CD11b+Ly6G+Ly6C−) as well as CD19+ dendritic cells. This corresponded with the suppression of the ongoing immune response measured by the reduction of pathogenic cytokines IL-10 and IL-13, as well as IL-17 and IFNγ, in comparison to other treatment groups. As chronic inflammation is generally associated with the accumulation of MDSCs, this study may enable the rational design of cost-effective, safe, and scalable delivery systems for the treatment of inflammation-mediated diseases.

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Myeloid‐derived suppressor cells in the therapy of autoimmune diseases

Bekić,

Tomić

2023

Eur J Immunol

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Myeloid‐derived suppressor cells (MDSCs) are well recognised as critical factors in the pathology of tumours. However, their roles in autoimmune diseases are still unclear, which hampers the development of efficient immunotherapies. The role of different MDSCs subsets in multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus displayed different mechanisms of immune suppression, and several studies pointed to MDSCs’ capacity to induce T helper (Th)17 cells and tissue damage. These results also suggested that MDSCs could be present in different functional states and utilise different mechanisms for controlling the activity of T and B cells. Therefore, various therapeutic strategies should be employed to restore homeostasis in autoimmune diseases. The therapies harnessing MDSCs could be designed either as cell therapy or rely on the expansion and activation of MDSCs in vivo or their depletion. Cumulatively, MDSCs are inevitable players in autoimmunity, and rational approaches in developing therapies are required to avoid the adverse effects of MDSCs and harness their suppressive mechanisms to improve the overall efficacy of autoimmunity therapy.This article is protected by copyright. All rights reserved

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Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients

Cited by 52 publications

References 29 publications

Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model

Myeloid‐derived suppressor cells in the therapy of autoimmune diseases

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