RESUMO
B cells and in particular IL-10-secreting B cells emerge as important players in immune balance during pregnancy. We have recently revealed that CD19-deficient (CD19-/-), B cell-specific IL-10-deficient (BIL-10-/-) and B cell-deficient µMT pregnant mice are highly susceptible to LPS-induced preterm birth (PTB). We aimed to analyze the ability of IL-10-secreting cells to protect from PTB and the underlying mechanisms. Wild type (WT), CD19-/-, BIL-10-/- and µMT mice were treated with LPS at gd16 and the cellular immune response was investigated 24 h later. LPS-treated BIL-10-/- dams showed a more pronounced PTB phenotype compared to WT, CD19-/- and µMT females, and increased inflammatory and reduced anti-inflammatory mediator concentrations in the peritoneal cavity and serum. CD19-/-, BIL-10-/- and µMT mice displayed altered immune cell population frequencies in the blood and uterus with lower numbers of IL-10-secreting B cells and T cells. BIL-10-/- mothers presented decreased frequencies of uterine CD4+CD25+Foxp3+ Treg cells. Co-stimulatory molecules are critical for feto-maternal tolerance and IL-10 secretion. We found dysregulated PD-1 expression in peripheral blood and ICOS expression in the uterus of CD19-/-, BIL-10-/- and µMT dams. Our data show that B cell-specific IL-10-signaling is essential for a balanced maternal immune response to an inflammatory stimulant that cannot be hampered without IL-10-secreting B cells.
Assuntos
Linfócitos B , Interleucina-10 , Nascimento Prematuro , Animais , Antígenos CD19/metabolismo , Linfócitos B/metabolismo , Feminino , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Recém-Nascido , Interleucina-10/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Gravidez , Nascimento Prematuro/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T ReguladoresRESUMO
OBJECTIVE: To detect the expression level of ICOS on Th9 cells in mice infected with Schistosoma japonicum, and investigate the relation between ICOS signaling and Th9 cell polarization. METHODS: Twenty-five mice with S. japonicum infection were used as models. IL-9+cells in CD4+ T cells and ICOS+ cells in Th9 cells of the mice were detected by flow cytometry 0, 4, 7, 9 weeks and 12 weeks after the infection. RESULTS: Compared with that 0 week after the infection, the proportion of Th9 cells in CD4+ T cells of the mice significantly increased 4, 7, 9, 12 weeks after the infection (all P < 0.05), and the proportion of ICOS+ cells in Th9 cells also markedly improved (P < 0.05). CONCLUSIONS: In S. japonicum infection, the ICOS signaling may have a regulatory effect on Th9 cell polarization.
Assuntos
Linfócitos T CD4-Positivos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Esquistossomose Japônica , Transdução de Sinais , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Interações Hospedeiro-Parasita/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma japonicum , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/fisiopatologiaRESUMO
To detect the expression level of ICOS on Th9 cells in mice infected with Schistosoma japonicum, and investigate the relation between ICOS signaling and Th9 cell polarization.Twenty-five mice with S. japonicum infection were used as models. IL-9+cells in CD4+ T cells and ICOS+ cells in Th9 cells of the mice were detected by flow cytometry 0, 4, 7, 9 weeks and 12 weeks after the infection.Compared with that 0 week after the infection, the proportion of Th9 cells in CD4+ T cells of the mice significantly increased 4, 7, 9, 12 weeks after the infection (all P < 0.05), and the proportion of ICOS+ cells in Th9 cells also markedly improved (P < 0.05).In S. japonicum infection, the ICOS signaling may have a regulatory effect on Th9 cell polarization.
