Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-κB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10−/− mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity

MicroRNA and NF1 Tumorigenesis

© 2012 Springer-Verlag Berlin Heidelberg. All rights are reserved. MicroRNAs (miRNAs) are short (20-23-nucleotide), endogenous, single-stranded RNA molecules that regulate gene expression. Aberrant miRNA expression signatures are hallmarks of different diseases, including cancer, in which they can function as oncogenes or tumour suppressor genes (TSG). Despite the rarity of studies involving miRNAs conducted in peripheral nerve sheath tumours, several interesting candidate miRNAs, including miR-34a, miR-29c, miR-10b and miR-214, have been identified for which there is evidence for involvement in the progression of neurofibromas to malignant peripheral nerve sheath tumours (MPNST). Inactivation of p53 mediates at least some of its loss of tumour suppressor function through miRNA, with miR-34a playing a pivotal role in this process. MiR-29c, which also functions as a TSG, is expressed at a lower level in MPNST compared to neurofibromas, in a study confined to patients with neurofibromatosis type 1. MiR-29c plays a role in tumour invasion and migration via regulation of the extracellular matrix component including metalloproteinase and collagen genes. Conversely, miR-10b and miR-214 act as oncogenes in nerve sheath tumours. MiR-10b was shown to decrease significantly cell proliferation, migration and invasion whereas miR-214, known to be regulated by TWIST1, a transcription factor playing a role in metastatic progression, is highly expressed in MPNST compared to neurofibromas. Deregulation of miRNA plays an important role in the transformation of benign to MPNST arising both in individuals with and without neurofibromatosis type 1