Myeloid-Derived Suppressor Cells Play Crucial Roles in the Regulation of Mouse Collagen-Induced Arthritis

Abstract

Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. The role of MDSCs in autoimmune diseases remains controversial, and little is known about the function of MDSCs in autoimmune arthritis. In this study, we clarify that MDSCs play crucial roles in the regulation of proinflammatory immune response in a collagen-induced arthritis (CIA) mouse model. MDSCs accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4+ T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited the production of IFN-γ, IL-2, TNF-α, and IL-6 by CD4+ T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced the severity of CIA in vivo, which was accompanied by a decrease in the number of CD4+ T cells and Th17 cells in the draining lymph nodes. However, depletion of MDSCs abrogated the spontaneous improvement of CIA. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the proinflammatory immune response of CD4+ T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.

Mesenchymal Stem/Stromal Cells Protect against Autoimmunity via CCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells

“…Although MDSCs have a deleterious role in cancer by inhibiting antitumor immunity (10)(11)(12)(13), it is possible that the cells have beneficial effects in autoimmunity by limiting T cell responses (8,14). In support of this possibility, recent studies have demonstrated that MDSCs accumulate in tissues with autoimmune diseases, including multiple sclerosis (15)(16)(17), inflammatory bowel disease (18,19), uveoretinitis (20), collagen-induced arthritis (21), and type 1 diabetes (22). However, the role of MDSCs in autoimmune diseases is not fully elucidated (14).…”

Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of tregs and attenuation of rheumatoid inflammation in mice

“…SCIenTIfIC RepoRts | (2018) 8:3753 | DOI:10.1038/s41598-018-21856-2 previous report 12 . The percentages of both M-MDSCs and G-MDSCs were also significantly higher in CIA mice on day 35 in both peripheral blood and spleen (Fig.…”

“…Given the potent immuoregulatory activity of MDSCs, it could be expected that MDSCs could have therapeutic impact on RA. There have been discordant results regarding the effect of MDSCs on RA [12][13][14][15][16][17][18][19] . However, all the previous papers performed adoptive transfer of MDSCs in animal model of RA to verify whether the MDSCs had therapeutic effects on RA.…”

“…have therapeutic effects in animal model of RA [12][13][14][15][16] . However, a few recent papers have shown that MDSCs can aggravate inflammatory arthritis in mice [17][18][19] .…”

Suppressor Cells – The Basis of Immunopathogenesis Autoimmune Diseases

“…Накоп-лены четкие данные об их определяющей роли в подавлении активности иммунокомпетентных клеток при опухолевом росте [18]. Что касается аутоиммунной патологии, то определенно можно говорить о наличии их при данных заболеваниях, о возможности подавления развития аутоиммун-ных процессов с помощью введения этих клеток в эксперименте [12,13,17]. И в то же время име-ются противоречивые данные об изменении их количества при этих патологиях.…”