ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.