ABSTRACT
BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. METHODS: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. RESULTS: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. CONCLUSION: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.
ANTECEDENTES: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. OBJETIVOS: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. MÉTODOS: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. RESULTADOS: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. CONCLUSIÓN: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mice , Animals , Toll-Like Receptor 4/genetics , Mice, Knockout , Chimerism , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Acute DiseaseABSTRACT
Drawing upon data from the China Labor-force Dynamics Survey (CLDS) of 2012 and 2014, this paper uses the panel binary choice model to examine the determinants of the settlement intentions of rural-urban migrants. Results showed that both a sense of belonging and social identity play important roles in determining rural-urban migrants settlement decisions. Besides these, wage, education, and health also affect the willingness of migrant workers to settle in a given area. Therefore, to promote urbanization, policy-makers should pay attention to the subjective demands of rural-urban migrants. We suggested that decision- and policy-makers help such migrants improve their social networks and eliminate identity discrimination, so as to encourage their willingness to settle in cities.(AU)
Com base nos dados do Laboratório de Dinâmica da Força de Trabalho da China (CLDS) de 2012 e 2014, este artigo usa o modelo de escolha binária do painel para examinar os determinantes das intenções de assentamento de migrantes rurais-urbanos. Os resultados mostram que tanto o senso de pertencimento, quanto a identidade social, desempenham papéis importantes na determinação das decisões de assentamentos de migrantes rurais-urbanos. Além destes, salário, educação e saúde também afetam a disposição dos trabalhadores migrantes de se estabelecerem em uma determinada área. Portanto, a fim de promover a urbanização, os formuladores de políticas devem prestar atenção às demandas subjetivas dos migrantes rurais-urbanos. Sugerimos que autoridades e formuladores de políticas públicas ajudem esses migrantes a melhorar sua rede social e a eliminar a discriminação de identidade, de modo a incentivar sua disposição de se estabelecer nas cidades.(AU)
Subject(s)
Humans , Transients and Migrants/psychology , Social Identification , Human Settlements/analysis , ChinaABSTRACT
ABSTRACT: Drawing upon data from the China Labor-force Dynamics Survey (CLDS) of 2012 and 2014, this paper uses the panel binary choice model to examine the determinants of the settlement intentions of rural-urban migrants. Results showed that both a sense of belonging and social identity play important roles in determining rural-urban migrants' settlement decisions. Besides these, wage, education, and health also affect the willingness of migrant workers to settle in a given area. Therefore, to promote urbanization, policy-makers should pay attention to the subjective demands of rural-urban migrants. We suggested that decision- and policy-makers help such migrants improve their social networks and eliminate identity discrimination, so as to encourage their willingness to settle in cities.
RESUMO: Com base nos dados do Laboratório de Dinâmica da Força de Trabalho da China (CLDS) de 2012 e 2014, este artigo usa o modelo de escolha binária do painel para examinar os determinantes das intenções de assentamento de migrantes rurais-urbanos. Os resultados mostram que tanto o senso de pertencimento, quanto a identidade social, desempenham papéis importantes na determinação das decisões de assentamentos de migrantes rurais-urbanos. Além destes, salário, educação e saúde também afetam a disposição dos trabalhadores migrantes de se estabelecerem em uma determinada área. Portanto, a fim de promover a urbanização, os formuladores de políticas devem prestar atenção às demandas subjetivas dos migrantes rurais-urbanos. Sugerimos que autoridades e formuladores de políticas públicas ajudem esses migrantes a melhorar sua rede social e a eliminar a discriminação de identidade, de modo a incentivar sua disposição de se estabelecer nas cidades.
ABSTRACT
Drawing upon data from the China Labor-force Dynamics Survey (CLDS) of 2012 and 2014, this paper uses the panel binary choice model to examine the determinants of the settlement intentions of rural-urban migrants. Results showed that both a sense of belonging and social identity play important roles in determining rural-urban migrants settlement decisions. Besides these, wage, education, and health also affect the willingness of migrant workers to settle in a given area. Therefore, to promote urbanization, policy-makers should pay attention to the subjective demands of rural-urban migrants. We suggested that decision- and policy-makers help such migrants improve their social networks and eliminate identity discrimination, so as to encourage their willingness to settle in cities.
Com base nos dados do Laboratório de Dinâmica da Força de Trabalho da China (CLDS) de 2012 e 2014, este artigo usa o modelo de escolha binária do painel para examinar os determinantes das intenções de assentamento de migrantes rurais-urbanos. Os resultados mostram que tanto o senso de pertencimento, quanto a identidade social, desempenham papéis importantes na determinação das decisões de assentamentos de migrantes rurais-urbanos. Além destes, salário, educação e saúde também afetam a disposição dos trabalhadores migrantes de se estabelecerem em uma determinada área. Portanto, a fim de promover a urbanização, os formuladores de políticas devem prestar atenção às demandas subjetivas dos migrantes rurais-urbanos. Sugerimos que autoridades e formuladores de políticas públicas ajudem esses migrantes a melhorar sua rede social e a eliminar a discriminação de identidade, de modo a incentivar sua disposição de se estabelecer nas cidades.
Subject(s)
Humans , Human Settlements/analysis , Social Identification , Transients and Migrants/psychology , ChinaABSTRACT
Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.
Subject(s)
Leukocytes, Mononuclear/chemistry , Macrophage Migration-Inhibitory Factors/metabolism , RNA, Messenger/metabolism , Vitiligo/metabolism , Adolescent , Adult , Case-Control Studies , Enzyme-Linked Immunospot Assay , Female , Humans , Macrophage Migration-Inhibitory Factors/analysis , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Vitiligo/etiology , Vitiligo/pathology , Young AdultABSTRACT
Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.