Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Objective:To investigate the effects of IL-28B in a mouse model of dextran sulfate sodium (DSS)-induced colitis and to analyze the possible mechanism.Methods:Thirty-five male C57BL/6 mice were randomly divided into the following groups with seven mice in each group: control group, DSS group and three IL-28B groups (1.25 μg, 2.5 μg and 5 μg). The mice in the DSS group and IL-28B groups were fed with 2.5% DSS solution and from day 3, the IL-28B groups were given intraperitoneal injection of corresponding IL-28B every day and the DSS group was treated with PBS. During the experiment, the disease activity index (DAI) was evaluated daily. On day 8, the mice were sacrificed and peripheral blood, spleen, mesenteric lymph node and colon samples were collected. The colon samples were observed, measured in length and stained with HE, and histopathological scores were calculated based on HE staining. Changes of immune cells in different samples were detected by flow cytometry. ELISA was used to detect the expression of IL-12, IL-10, IL-1β, IL-6, IL-4 and IL-13 in serum and colon tissues.Results:Compared with the DSS group, the IL-28B group (2.5 μg) had lower DAI scores [(9.40±1.67) vs (3.50±1.73), P<0.01], less shortening of the colon [(5.16±0.61) cm vs (6.91±0.60) cm, P<0.01] and significantly lower histopathological scores [(7.33±0.58) vs (4.33±0.58), P<0.01]. Moreover, compared with the DSS group, the IL-28B group (2.5 μg) showed decreased macrophages in the peripheral blood [(21.39±3.21)% vs (15.63±2.98)%, P<0.05] and spleen [(3.03±0.28)% vs (2.05±0.48)%, P<0.05], and significantly increased mean fluorescence intensity of M2 macrophages in the colon [(1 361.00±293.40) vs (2 074.00±87.61), P<0.05]. IL-12 expression in colon tissues and IL-1β expression in serum were reduced, and IL-10, IL-4 and IL-13 expression in colon tissues was significantly increased in the IL-28B group (2.5 μg) as compared with those in the DSS group [IL-12: (31.72±6.92) pg/mg vs (5.41±3.41) pg/mg; IL-1β: (48.01±16.13) pg/ml vs (12.27±6.26) pg/ml; IL-10: (184.70±46.82) pg/mg vs (444.30±157.80) pg/mg; IL-4: (2.23±0.27) pg/mg vs (3.64±0.80) pg/mg; IL-13: (11.79±0.99) pg/mg vs (22.59±1.92) pg/mg; all P<0.05]. Conclusions:IL-28B might alleviate the severity of acute enteritis in mice by increasing the secretion of IL-4 and IL-13, regulating macrophage differentiation and modulating the expression of inflammatory factors.

Objective:To investigate the related mechanism of IL-17B in regulating host immune response by studying the role and mechanism of IL-17B in the infection of Listeria monocytogenes in mice. Methods:Eighteen male C57BL/6 mice were randomly divided into three groups with six in each group: control group, PBS group and wild-type (WT) group. The control group was not given any treatment. The mice in the PBS group were injected with 100 μl of sterile PBS, while C57BL/6 mice in the WT group and IL-17B deficient (IL-17B -/-) male mice were injected intravenously with 100 μl of Listeria monocytogenes 19115 (2×10 4 colony forming unit). The mice were sacrificed 48 h after infection and then peripheral blood, spleen and liver samples were collected. Bacterial colonization in mouse spleen and liver was detected by plate count method; HE staining was used to evaluate histopathological damages; flow cytometry was used to detect the immune cells in different tissues. ELISA and qRT-PCR were used to detect the levels of IL-1β, IL-6, IL-12p40, TNF-α, IFN-γ and iNOS in serum and spleen. qRT-PCR were used to detect the expression of IL-17B and IL-17RB. Results:Bacterial colonization in mouse spleen was reduced in the IL-17B -/- group as compared with that in the WT group ( P<0.05). Compared with the PBS group, Listeria monocytogenes infection increased the expression of IL-17B and IL-17RB in mouse spleen ( P<0.05, P<0.01). There was no significant difference in the pathological damages in spleen between WT and IL-17B -/- groups. Moreover, compared with the WT group, the IL-17B -/- group showed increased macrophages, M1 macrophages ( P<0.01) and NK cells ( P<0.05) in spleen, up-regulated macrophages ( P<0.05) and M1 macrophages ( P<0.01) in the peripheral blood, enhanced expression of IL-6 in serum and spleen ( P<0.05), and promoted expression of IL-6, IL-12, IL-1β, TNF-α, IFN-γ and iNOS in spleen. Conclusions:IL-17B might inhibit Listeria monocytogenes clearance by inhibiting macrophage infiltration and the secretion of IL-6.

Background and Objectives: Human umbilical cord mesenchymal stem cells (HUC-MSCs) are promising candidates for cell-based therapy in regenerative medicine or other diseases due to their superior characteristics, including higher proliferation, faster self-renewal ability, lower immunogenicity, a noninvasive harvest procedure, easy expansion in vitro, and ethical access, compared with stem cells from other sources. Methods: and Results: In the present study, we knocked down the expression of SOX9 in HUC-MSCs by lentivirus interference and found that knockdown of SOX9 inhibited the proliferation and migration of HUC-MSCs and influenced the expression of cytokines (IL-6 and IL-8), growth factors (GM-CSF and VEGF) and stemness-related genes (OCT4 and SALL4). In addition, the repair effect of skin with burn injury in rats treated with HUC-MSCs transfected with sh-control was better than that rats treated with HUC-MSCs transfected with shSOX9 or PBS, and the accessory structures of the skin, including hair follicles and glands, were greater than those in the other groups. We found that knockdown of the expression of SOX9 obviously inhibited the expression of Ki67, CK14 and CK18. Conclusions In conclusion, this study will provide a guide for modifying HUC-MSCs by bioengineering technology in the future.

Objective: To investigate the role of CD11b agonist leukadherin-1 (LA1) in the development of intestinal inflammation and colitis disease in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Methods: The mouse model of experimental colitis was induced by DSS. Body weight changes and survival status were monitored every day. The length of colons was measured at day 7. Colon tissue sections were stained with hematoxylin and eosin (HE) and observed under an optical microscope for pathological analysis. The percentages of apoptotic cells in colon tissues were observed by TUNEL staining. Myeloperoxidase (MPO) activity was measured with MPO activity detection kit. IL-1β and TNF-α levels were detected by ELISA. Macrophages and TNF-α in colon tissues were observed using immunofluorescence staining and confocal microscopy. Flow cytometry was performed to detect the changes in TLR4 expression on macrophages after stimulating mice with LA1 for 0, 3, 6 and 12 h. Moreover, TLR4 expression was also measured by Western blot after treating bone marrow-derived macrophages (BMDMs) with LA1 for 0, 3, 6 and 12 h. Unpaired t-test was used for statistical analysis. Results: Compared with the DSS group, the LA1+ DSS group presented lower mortality rate, greater body weight and longer colon and the differences between the two groups were statistically significant. Moreover, the LA1+ DSS group showed lighter pathological damages, decreased percentage of apoptotic cells and suppressed MPO activity as compared with those of the DSS group. The number of macrophages and the relative concentrations of IL-1β and TNF-α in colon tissues were lower in the LA1+ DSS group than in the DSS group, and the differences between the two groups were statistically significant. There was no significant difference in the total expression of TLR4 on macrophages before and after LA1 treatment. However, the mean flourscence indensity (MFI) of TLR4 was weaker on the LA1-treated macrophages than on the untreated macrophages. Conclusions LA1 could alleviate the DSS-induced experimental colitis in mice through suppressing the activation of TLR4 pathway on macrophages. This study provided a new insight and theoretical reference for understanding the pathogenesis of inflammatory bowel diseases.