ABSTRACT
PreB cell leukemia homeobox 1 (Pbx1)-d is a dominant-negative splice isoform of the gene Pbx1 that corresponds to the NZM2410 lupus susceptibility locus Sle1a1. Pbx1 is required to maintain stem cell self-renewal, including that of mesenchymal stem cells (MSCs). MSCs have immunosuppressive functions that require stem cell maintenance. We tested the hypothesis that the expression of Pbx1-d favors MSC differentiation and impairs their immunosuppressive functions. We demonstrate that Sle1a1 MSCs express high levels of Pbx1-d as compared with congenic C57BL/6J (B6) MSCs. Sle1a1 MSCs grew faster and differentiated significantly more rapidly into osteoblasts than did B6 MSCs. This corresponded to a significant decrease in the expression of genes associated with stemness and an increase in the expression of genes associated with differentiation. Additionally, Sle1a1 MSCs express a gene expression profile associated with an enhanced innate immunity and inflammation. Suppression of Ig production from TLR-activated B6 B cells and IL-2 secretion from activated B6 CD4+ T cells was significantly impaired in Sle1a1 MSCs as compared with B6 MSCs. B6.Sle1a1 MSCs showed intermediate activity in suppressing lupus immunophenotypes in three different mouse models. Taken together, these data suggest that the expression of the lupus susceptibility allele Pbx1-d isoform impairs MSC functions, which may contribute to lupus pathogenesis both through a defective immunosuppression and the promotion of a proinflammatory environment.
Subject(s)
Autoimmunity/immunology , CD4-Positive T-Lymphocytes/immunology , Cell Differentiation/genetics , Homeodomain Proteins/genetics , Immune Tolerance/immunology , Mesenchymal Stem Cells/cytology , Osteoblasts/cytology , Transcription Factors/genetics , Animals , Autoimmunity/genetics , Gene Expression , Homeodomain Proteins/biosynthesis , Immunoglobulins/biosynthesis , Immunologic Memory/immunology , Inflammation/immunology , Interleukin-2/metabolism , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/pathology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BL , Pre-B-Cell Leukemia Transcription Factor 1 , Protein Isoforms/genetics , Toll-Like Receptors/immunology , Transcription Factors/biosynthesisABSTRACT
BACKGROUND: Research regarding the relationship between preceptorship and development of critical thinking in new graduate nurses is sparse. No studies could be found that examined the relationship of preceptor education to critical thinking scores of new graduate nurses. METHODS: A quasi-experimental, mixed-methods design measured critical thinking ability of new graduate nurses. Focus group interviews were conducted with preceptors who attended an author-developed educational program. RESULTS: Preceptors' participation in the educational session contributed to the evaluation subscale of critical thinking skills of the experimental group on the California Critical Thinking Skills Test (F = 4.709, p = .039). Preceptors had positive qualitative responses. CONCLUSIONS: Critical thinking skills of new graduate nurses can be improved and learning relationships developed through preceptor education. Further study is suggested.
