Autoimmune Diseases ; immunology ; Gene Expression Regulation ; immunology ; Humans ; Immunoglobulin G ; genetics ; immunology ; Sclerosis ; genetics ; immunology ; pathology

FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of FcγRIIB is also indispensable for its inhibitory function. Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE). In this review, we will summarize these epidemiological and functional studies of FcγRIIB-I232T in the past few years, and will further discuss the mechanisms accounting for the functional loss of FcγRIIB-I232T. Our review will help the reader gain a deeper understanding of the importance of the TM domain in mediating the inhibitory function of FcγRIIB and may provide insights to a new therapeutic target for the associated diseases.
Autoimmune Diseases ; drug therapy ; genetics ; immunology ; Humans ; Protein Domains ; Receptors, IgG ; chemistry ; immunology

HLA-Cw belongs to classic HLA-I gene, HLA-Cw molecules have high polymorphism like HLA-A and B molecules. They distribute extensively on the surfaces of karyote, not only presenting endogenetic antigen to CD8+ T cells to induce specific killing effect, but also participating in immunologic reaction as the ligands of killer cell immunoglobulin-like receptor (KIR). Thus it has been valued for their relations to diseases and the functions in transplantation immunity, anti virus and anti-tumor immunity.
Autoimmune Diseases ; immunology ; Graft vs Host Disease ; etiology ; HLA-C Antigens ; genetics ; physiology ; Humans ; Neoplasms ; immunology ; Receptors, Immunologic ; metabolism ; Receptors, KIR ; Virus Diseases ; immunology

Th17(T helper 17 cell), a newly discovered subset of T cells is associated with IL-23 and characterized by production of IL-17, the functions of which are distinct from those of Th1, Th2 and Treg subsets. The development of Th17 cells can be promoted by TGF-beta1, IL-6, and IL-23; but inhibited by IFN-gamma, IL-4 and Socs3. It is clear that Th17 cells have protective effects on body by facilitating the pro-inflammatory responses. On the other hand, the role of Th17 cells in the pathophysiology of autoimmune diseases has been described.
Autoimmune Diseases ; immunology ; physiopathology ; Interleukin-17 ; biosynthesis ; immunology ; Interleukin-23 ; biosynthesis ; genetics ; T-Lymphocyte Subsets ; immunology ; physiology ; T-Lymphocytes, Helper-Inducer ; classification ; cytology ; immunology ; Transforming Growth Factor beta1 ; biosynthesis ; genetics

Vav1, as a key downstream signaling molecule of T cell receptor, includes a catalytic core DH-PH-ZF domain with the function as guanine nucleotide exchange factor (GEF), and a SH3-SH2-SH3 domain with the function as adaptor protein. These two structures of Vav1 play different roles in the development, activation, proliferation and function of T cells, and thereby exert the different regulatory effect on the occurrence and development of autoimmune disease, graft rejection, cancer and other clinical conditions, implicating that Vav1 might be a potential therapeutic target for these diseases. This paper reviews the role of Vav1 in T cells and the occurrence of related diseases.
Adaptor Proteins, Signal Transducing ; Animals ; Autoimmune Diseases ; genetics ; physiopathology ; Humans ; Neoplasms ; genetics ; physiopathology ; Proto-Oncogene Proteins c-vav ; chemistry ; immunology ; metabolism ; T-Lymphocytes

OBJECTIVETo investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).

METHODSEAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.

RESULTSEAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.

CONCLUSIONTreatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.

Animals ; Animals, Genetically Modified ; Autoimmune Diseases ; immunology ; Bone Marrow Cells ; Cell Line ; Dendritic Cells ; immunology ; Genetic Therapy ; Immune Tolerance ; Interleukin-10 ; genetics ; immunology ; Myocarditis ; immunology ; Rats ; Rats, Inbred Lew

T cells recognize antigens through TCRs (T cell receptor). T cell clones can be sorted into 24 gene subfamilies based on the usage of the segments of TCR BV in gene rearrangement. Application of the various segments of TCR BV may establish TCR BV spectrotyping that can be used to analyze and recognize the different functional T cell clones, and understand the function and proliferation of various T cell clones in malignancy and autoimmune disease. In vitro expansion of a great deal of the specific antitumor T cells and transfusing them to patients will be able to develop a new method for tumor immunotherapy. Through analyze the character of the TCR BV gene, McAb against TCR or DNA vaccine to inhibit the growth of T cell clones associated-autoimmune disease and tumors might be developed. The McAb and vaccine may be used to cure these diseases. The commo T cells can also be modifed to specific antitumor T cells by method of TCR gene transfer. In this review, the characteristics of TCR, analysis method for gene spectrotyping of TCR BV, segments of TCR BV and autoimmue distase, T cell clones in hematologic maligrancies, recognition of T cell oligoclone expansion of T cells, and application of TCR BV gene spectrotyping in bone marrow transplantation were discussed and summarised.
Autoimmune Diseases ; genetics ; immunology ; Clone Cells ; cytology ; metabolism ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; genetics ; Hematologic Neoplasms ; genetics ; immunology ; Humans ; Receptors, Antigen, T-Cell ; classification ; genetics ; T-Lymphocyte Subsets ; cytology ; metabolism

BACKGROUNDExperimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.

METHODSEAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.

RESULTSBMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.

CONCLUSIONSIL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.

Animals ; Autoimmune Diseases ; immunology ; Dendritic Cells ; physiology ; Immune Tolerance ; Interleukin-10 ; genetics ; Lymphocyte Activation ; Male ; Myocarditis ; immunology ; Myosins ; immunology ; NF-kappa B ; physiology ; Rats ; Rats, Inbred Lew ; Signal Transduction ; Transfection

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The occurrence of common features of autoimmune diseases and the coassociation of multiple autoimmune diseases in the same individual or family supports the notion that there may be common genetic factors. METHODS: To investigate potential clustering of autoimmune thyroid disease (ATD) among type 1 diabetes patients and the contribution of common susceptibility genes to this, HLA DR/DQ alleles as well as antithyroid autoantibodies were measured in 115 Korean patients with type 1 diabetes and their 96 first-degree family members. RESULTS: Twenty-five percent of the patients had ATD, whereas 3 of 36 (8%) age-matched normal controls had ATD (RR = 3.7, p < 0.05). Twenty-six of ninty-six (27%) type 1 diabetes family members had ATD. No differences in the distribution of HLA alleles/haplotypes and genotypes between the patients with and without ATD were found. CONCLUSION: From this finding, we could assess that individuals with type 1 diabetes and their relatives frequently develop ATD, perhaps due to common susceptibility genes that are shared among first degree relatives.
Adult ; Alleles ; Autoantibodies/blood ; Autoimmune Diseases/epidemiology* ; Child ; Child, Preschool ; Diabetes Mellitus, Insulin-Dependent/genetics ; Diabetes Mellitus, Insulin-Dependent/complications* ; Female ; Glutamate Decarboxylase/immunology ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; Human ; Male ; Prevalence ; Thyroid Diseases/epidemiology*

To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.
Arthritis, Rheumatoid/*genetics/immunology/metabolism ; Autoimmune Diseases/genetics/immunology ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Genotype ; Humans ; Lupus Erythematosus, Systemic/genetics/immunology ; Microfilament Proteins/*genetics/metabolism ; Polymorphism, Genetic/*genetics ; Proteome/genetics ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization