RESUMEN
Mesenchymal stem cells (MSCs) have garnered attention for their regenerative and immunomodulatory capabilities in clinical trials for various diseases. However, the effectiveness of MSC-based therapies, especially for conditions like graft-versus-host disease (GvHD), remains uncertain. The cytokine interferon (IFN)-γ has been known to enhance the immunosuppressive properties of MSCs through cell-to-cell interactions and soluble factors. In this study, we observed that IFN-γ-treated MSCs upregulated the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), associated with immune evasion through the inhibition of natural killer (NK) cell cytotoxicity. To co-opt this immunomodulatory function, we generated MSCs overexpressing CEACAM1 and found that CEACAM1-engineered MSCs significantly reduced NK cell activation and cytotoxicity via cell-to-cell interaction, independent of NKG2D ligand regulation. Furthermore, CEACAM1-engineered MSCs effectively inhibited the proliferation and activation of T cells along with the inflammatory responses of monocytes. In a humanized GvHD mouse model, CEACAM1-MSCs, particularly CEACAM1-4S-MSCs, demonstrated therapeutic potential by improving survival and alleviating symptoms. These findings suggest that CEACAM1 expression on MSCs contributes to MSC-mediated regulation of immune responses and that CEACAM1-engineered MSC could have therapeutic potential in conditions involving immune dysregulation.
Asunto(s)
Antígenos CD , Moléculas de Adhesión Celular , Comunicación Celular , Enfermedad Injerto contra Huésped , Células Asesinas Naturales , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Animales , Antígenos CD/metabolismo , Humanos , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/terapia , Moléculas de Adhesión Celular/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Inmunomodulación , Ratones , Interferón gamma/metabolismo , Trasplante de Células Madre Mesenquimatosas , Proliferación Celular/efectos de los fármacos , Ingeniería Celular/métodosRESUMEN
This study aimed to investigate the effect of anger expression mode and meaning in life on mental health recovery among hospitalized patients with mental disorder in South Korea. Data were collected from 141 such patients using the Korean version of anger expression mode, meaning in life, and mental health recovery. Date were as analyzed using stepwise multiple regression analysis. Significant predictors of mental health recovery included presence of meaning, search for meaning, and anger control. The regression model explained 48.2% of mental health recovery. Interventions for fostering meaning in life and beneficial anger expression techniques may increase mental health recovery in this clinical population.