RESUMEN
BACKGROUND: Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. METHODS: In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. RESULTS: GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. CONCLUSIONS: This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.
Asunto(s)
Asma/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Células Dendríticas/metabolismo , Pyroglyphidae , Hipersensibilidad Respiratoria/metabolismo , Factores de Necrosis Tumoral/biosíntesis , Animales , Asma/sangre , Diferenciación Celular/fisiología , Niño , Técnicas de Cocultivo , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Hipersensibilidad Respiratoria/sangre , Factores de Necrosis Tumoral/sangreRESUMEN
Recent studies suggested that Traditional Chinese Medicine could play a beneficial role in conventional cancer treatment. The aim of this retrospective cohort study was to investigate the effect of Chinese herbal medicine (CHM) combined with Western medicine on the survival of patients with colorectal cancer. A retrospective cohort study was conducted on patients with newly diagnosed colorectal cancer identified from the Dalin Tzu Chi Hospital Cancer Registry Database in 2004-2014. Combining with the medical records of the study hospital, patients were classified into CHM users and CHM nonusers. Kaplan-Meier analyses and Cox proportional hazards regression analyses were used to investigate the survival between CHM users and CHM nonusers. A total of 535 patients with colorectal cancer were included in the study with 147 of them were CHM users. The log-rank test for Kaplan-Meier survival curve revealed a statistically significant difference between the survival of CHM users and CHM nonusers (P=0.006). Results from multivariate Cox regression analysis showed that CHM use was significantly associated with better survival (adjusted hazard ratio = 0.54, 95% CI = 0.38 to 0.77). In addition, the CHM formulae Jia Wei Xiao Yao San, Zhi Bah Di Huang Wan, Ping Wei San, and Qui Pi Tang were significantly associated with better survival. In conclusion, findings from this retrospective cohort study indicated that integrated CHM and Western medicine could improve survival in patients with colorectal cancer. Additional research on integrating TCM with Western medicine to improve cancer survival is warranted.