Biomedical subjects

Jau-Ling Suen

Publications and source records attributed to Jau-Ling Suen.

5 recordsLinked to original sources

PubMed2006

Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen-specific T cells and airway inflammation in a murine model of asthma.

T cells expressing a type-2 T helper profile of cytokines (Th2 cells) have been demonstrated to play an important role in the initiation and progression of allergic asthma, and it is well known that Fas ligand (FasL) induces apoptosis when bound to its receptor, Fas. In the present study, we examined the possibility of modulating asthma manifestations by dendritic cells (DCs) genetically engineered to express FasL (DC-FasL), which could deliver a death signal to T cells in an antigen-specific manner. The delivery of DC-FasL into ovalbumin (OVA)-immunized allergic mice decreased the airway hyper-responsiveness (AHR). Moreover, we established a mouse model of airway inflammation by using an adoptive transfer of Th2 cells derived from ovalbumin T cell receptor transgenic mice to study the effect of DC-FasL on airway reactivity. The administration of DC-FasL in Th2-cell-induced allergic mice had significantly decreased AHR, airway inflammation, and IL-4, IL-5 and IL-13 production. Furthermore, the numbers of OVA-specific T cells were decreased in the lung of mice receiving DC-FasL. These results demonstrate that FasL-expressing dendritic cells might be applied for the modulation of allergic responses.

Adenoviridae↗

PubMed2006

Morin promotes the production of Th2 cytokine by modulating bone marrow-derived dendritic cells.

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-alpha in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-gamma in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

Animals↗

PubMed2005

Identification of T-cell epitopes on U1A protein in MRL/lpr mice: double-negative T cells are the major responsive cells.

Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies such as anti-DNA, chromatin, histone, and ribonucleoprotein antibodies (Abs). Although the B-cell antigenic determinants have been well characterized, very limited data about the T-cell epitopes of self-antigen (Ag) have been reported. In the present study, we analysed auto-T-cell epitopes using bone marrow-derived dendritic cells (BM-DCs) pulsed with murine U1A (mU1A) protein capable of activating autoreactive T cells from unprimed MRL/lpr mice in vitro. The data suggested that there are at least four T-cell epitopes on the U1A protein, U1A31-50, U1A61-80, U1A201-220 and U1A271-287, and U1A31-50 had the most significant T-cell proliferative response. In addition, the main responsive T cells are the CD4- CD8- double-negative subgroup of T cells. Furthermore, we also demonstrated that the activation of double-negative T cells is major histocompatibility complex class II restricted. The study here provides information on T-cell epitope analysis of the U1A antigen using BM-DCs as the effective antigen-presenting cells.

Aging↗

PubMed2004

Treatment of murine lupus using nucleosomal T cell epitopes identified by bone marrow-derived dendritic cells.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies directed against intact nuclear structures, such as nucleosomes. The most prominent of these autoantibodies are those directed against double-stranded DNA (dsDNA) and histones. The majority are of the IgG isotype and show affinity maturation, both of which are known hallmarks of T cell help. Much evidence suggests that the nucleosome is a major candidate autoantigen in SLE. In this study, a novel strategy was used to identify the critical CD4+ T cell autoepitopes in nucleosomes. In addition, peptide-based therapy was then performed in a lupus animal model. METHODS: Bone marrow (BM)-derived dendritic cells (DCs) were used to examine the self-T cell responses against nucleosomes and to characterize the T cell epitope(s) of nucleosomes in (NZB x NZW)F1 (BWF1) mice. RESULTS: Several potential auto-T cell epitopes of core histone proteins (H2A, H2B, H3, and H4) were identified. Nucleosome-pulsed BM-derived DCs elicited release of interleukin-4 and interferon-gamma, representing a Th0 (i.e., mixed Th1 and Th2) pattern of cytokine production. In addition, intradermal immunization of BWF1 mice with the H3(111-130) peptide not only suppressed the level of anti-dsDNA and anti-single-stranded DNA IgG, but also significantly delayed the progress of glomerulonephritis in lupus-prone BWF1 mice. CONCLUSION: These results will help in understanding how pathogenic autoimmune responses develop in spontaneous SLE. This may potentially open the way to T cell-based immunotherapy for lupus.

Animals↗

PubMed2002

In vivo tolerance breakdown with dendritic cells pulsed with U1A protein in non-autoimmune mice: the induction of a high level of autoantibodies but not renal pathological changes.

One of the hallmarks of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), is the immune response to nuclear autoantigens. Several studies have proposed that dendritic cells may acquire the nuclear autoantigens from the apoptotic cells to initiate the systemic autoimmune responses. To examine the immune response to a nuclear autoantigen induced by dendritic cells, bone marrow-derived dendritic cells (BMDCs) pulsed with U1 small nuclear ribonucleoprotein (snRNP)-A protein (U1A) were intravenously injected into non-autoimmune mice. The results showed that BMDCs pulsed with U1A proteins by intravenous injection into BALB/c (H-2d) and DBA-2xNZW F1 (H-2d/u) mice were capable of activating the autoreactive T cells and inducing a high titre of immunoglobulin G (IgG) anti-U1A antibodies. Both groups of mice with a high anti-U1A autoantibody titre also transiently developed IgG against double-stranded (ds) DNA. However, unlike NZBxNZW F1 (BWF1) (H-2d/u) mice, no obviously histopathological changes to the glomeruli were noted in the mice treated either with BMDCs or with U1A-pulsed BMDCs. Several months after immunization, all mice treated with U1A-pulsed BMDCs did develop IgG, but not the complement C3 deposit in the glomeruli. The cytokine profile produced by the U1A-specific T cells of primed DBA-2xNZW F1 mice was skewed toward the T helper type 1 phenotype compared with that of BWF1 mice. The model we describe here adds to the further understanding of the pathogenic mechanisms, such as self-antigen shifting, and the mechanisms that account for the different responses to self-antigens when in a normal or an autoimmune state.

Animals↗