Lentiviral-mediated HoxB4 expression in human embryonic stem cells initiates early hematopoiesis in a dose-dependent manner but does not promote myeloid differentiation.

The variation of HoxB4 expression levels might be a key regulatory mechanism in the differentiation of human embryonic stem cell (hESC)-derived hematopoietic stem cells (HSCs). In this study, hESCs ectopically expressing high and low levels of HoxB4 were obtained using lentiviral gene transfer. Quantification throughout differentiation revealed a steady increase in transcription levels from our constructs.

Stromal cells and osteoclasts are responsible for exacerbated collagen-induced arthritis in interferon-beta-deficient mice.

Objective: Clinical trials using interferon-beta (IFNbeta) in the treatment of rheumatoid arthritis have shown conflicting results. We undertook this study to understand the mechanisms of IFNbeta in arthritis at a physiologic level.

Methods: Collagen-induced arthritis (CIA) was induced in IFNbeta-deficient and control mice.

Intrinsic tolerance in autologous collagen-induced arthritis is generated by CD152-dependent CD4+ suppressor cells.

Collagen-induced arthritis is a mouse model of rheumatoid arthritis (RA) and is commonly induced after immunization with type II collagen (CII) of a non-mouse origin. T cell recognition of heterologous CII epitopes has been shown to be critical in development of arthritis, as mice with cartilage-restricted transgenic expression of the heterologous T cell epitope (MMC mice) are partially tolerized to CII. However, the mechanism responsible for tolerance and arthritis resistance in these mice is unclear.

Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

Background: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known.

IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis.

Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells to proliferate or produce IFN-gamma in response to recall Ag.

Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene.

Background: IFN-beta has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a T(H)2 response. However, other studies have suggested that endogenous type I IFN might downregulate the allergic response in mice.

Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.

Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively.

Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection.

Collagen-induced arthritis (CIA) is induced in H-2(q) mice after immunization with rat type II collagen (CII). The immunodominant T cell epitope on heterologous CII has been located to CII256-270. We have previously shown that TSC transgenic mice, which express the heterologous epitope in type I collagen (CI), e.