Abstract:
:Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive swelling and erythema by arthritogenic antibody injection, whereas Tyk2-deficient mice did not show any signs of arthritis. Indeed, neither the infiltration of inflammatory cells nor the fibrillation of articular cartilages was observed in Tyk2-deficient mice. Tyk2 deficiency also reduced the production of T(h)1/T(h)17-related cytokines, the other proinflammatory cytokines and matrix metalloproteases, which are induced in the CAIA paw. Our results demonstrate a critical contribution of Tyk2 in the development of arthritis, and we propose that Tyk2 might be an important candidate for drug development.
journal_name
Int Immunoljournal_title
International immunologyauthors
Ishizaki M,Muromoto R,Akimoto T,Ohshiro Y,Takahashi M,Sekine Y,Maeda H,Shimoda K,Oritani K,Matsuda Tdoi
10.1093/intimm/dxr057subject
Has Abstractpub_date
2011-09-01 00:00:00pages
575-82issue
9eissn
0953-8178issn
1460-2377pii
dxr057journal_volume
23pub_type
杂志文章abstract::The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point o...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.10.1349
更新日期:1993-10-01 00:00:00
abstract::Dendritic cells (DC) are key players in the initiation and modulation of adaptive immune responses due to their ability to acquire and present antigen and stimulate T cells. For the induction of effector T cell functions, antigen must be presented by activated DC. In this study, we have compared uptake of antigen by m...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp053
更新日期:2009-07-01 00:00:00
abstract::Previous evidence from several laboratories suggests that CD8+ T suppressor cells may be important regulatory elements governing specific unresponsiveness of lepromatous lepromatous leprosy patients to M.leprae. To analyse the mechanism of suppression, CD8+ Ts clones were established from lesions and peripheral blood ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/1.2.121
更新日期:1989-01-01 00:00:00
abstract::Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno-pathogenic peptides. Recent...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1229
更新日期:1998-08-01 00:00:00
abstract::CD100/Sema4D belongs to the semaphorin family, factors known to act as repulsive cues for axons during neuronal development. Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72. It remains controversial, however, whether human CD100 can function thro...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg098
更新日期:2003-08-01 00:00:00
abstract::The transcription factor interferon regulatory factor-5 (IRF5) plays an important role in innate immune responses via the TLR-MyD88 (Toll-like receptor - myeloid differentiation primary response 88) pathway. IRF5 is also involved in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Recent ...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxy032
更新日期:2018-10-29 00:00:00
abstract::Based on the similarity in primary structure between the newly characterized ligand for CD40 (CD40L) and the tumor necrosis factors (TNFs), we have modeled a detailed 3-D structure for CD40L. We used the known structure of TNF alpha as a template for the generation of the CD40L model. The soundness of the model-buildi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.2.233
更新日期:1993-02-01 00:00:00
abstract::The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of apoptotic cell death, whereas Bax facilitates it, indicating possible interac...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.11.1817
更新日期:1995-11-01 00:00:00
abstract::CD4 T cells are not thought to play a significant role in generating an effective primary CD8 T cell response to most viral infections. We have challenged this view by demonstrating that antigen-specific CD4 T cells can indeed suppress the proliferation of antigen-specific naive CD8 T cells in response to low doses of...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl061
更新日期:2006-08-01 00:00:00
abstract::CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh367
更新日期:2006-02-01 00:00:00
abstract::Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human no...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn038
更新日期:2008-07-01 00:00:00
abstract::Whether astrocytes utilize B7:CD28 co-stimulation to activate T cells mediating CNS inflammatory disease is controversial. In this report, primary astrocytes and murine astrocyte lines, generated by immortalization at two different times, day 7 or 45 of culture, were examined for their capability to express B7 co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.7.1169
更新日期:1999-07-01 00:00:00
abstract::SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1049
更新日期:1998-08-01 00:00:00
abstract::House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoide...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl065
更新日期:2006-08-01 00:00:00
abstract::Recent data suggest that initiation of signal transduction via type 1 Fc epsilon receptor (Fc epsilon RI) and other immunoreceptors is spatially constrained to lipid rafts. In order to better understand the complexity and function of these structures, we prepared mAb against lipid rafts from the rat basophilic leukemi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/14.2.213
更新日期:2002-02-01 00:00:00
abstract::Impaired lymphocyte function is a common feature of human diabetes. Nucleoside transport across the plasma membrane is an essential step during lymphocyte growth and activation. In our study, we evaluated the impact of diabetic conditions on nucleoside transport system in B lymphocytes. Examination of the nucleoside t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh195
更新日期:2005-02-01 00:00:00
abstract::NK cells limit the emergence of cancers and viral infections by surveillance of 'missing-self' and 'induced-self' ligands, and by direct recognition of pathogen-associated molecules. We examined individual roles for Toll-like receptors (TLRs)-7 and -8 in human NK-cell activation using synthetic, small molecule agonist...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl046
更新日期:2006-07-01 00:00:00
abstract::The intestinal epithelium not only acts as the physical structure that separates the intestinal lumen from the body but also actively participates in intestinal barrier functions. In the past decade, significant progress has been made in the development of culture technologies to maintain intestinal epithelial cells (...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxy065
更新日期:2019-02-06 00:00:00
abstract::Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cel...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn078
更新日期:2008-09-01 00:00:00
abstract::IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates Th1 responses by inducing the development of CD4+, IFN-gamma producing Th1 T cells in mouse and human. We have previously reported that allergen-specific CD4+ Th2 T cell clones produce IFN-gamma, following activation b...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.7.1091
更新日期:1994-07-01 00:00:00
abstract::We have found that FOXP3 is an oligomeric component of a large supramolecular complex. Certain FOXP3 mutants with single amino acid deletions in the leucine zipper domain of FOXP3 are associated with the X-linked autoimmunity-allergic dysregulation (XLAAD) and immunodysregulation, polyendocrinopathy and enteropathy, X...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm043
更新日期:2007-07-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.6.673
更新日期:1992-06-01 00:00:00
abstract::Peyer's patch (PP) organogenesis proceeds through three histologically distinct steps: formation of organizing centers expressing VCAM-1 and ICAM-1 in segregated regions of the intestine at 15.5 days post-coitus (d.p.c.) (step I), accumulation of blood cells expressing different sets of surface markers to this region ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.643
更新日期:1999-05-01 00:00:00
abstract::It was recently shown that paf-acether (paf) synthesized in different cell types remains partly cell-associated. In the present work, we tested the hypothesis that cell-associated paf might in fact remain exposed on the external plasma membrane and be able to exert its biological functions. Human polymorphonuclear neu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.11.1157
更新日期:1991-11-01 00:00:00
abstract::Germline CH transcripts initiate from a non-coding I exon and terminate downstream of the associated CH exons. Ig heavy chain class switch recombination from the VDJ-C mu gene to particular downstream CH genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline CH transcrip...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.4.491
更新日期:1994-04-01 00:00:00
abstract::CD70 and CD80 are co-stimulatory molecules which belong to the tumor necrosis factor family and the B7 family respectively. When they are co-expressed by gene-modified TS/A tumor cells, they provide an efficient protective and long-lasting T-dependent antitumor response. We first showed that when CD70 and CD80 were de...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg038
更新日期:2003-03-01 00:00:00
abstract::Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors cultured in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC) and have been shown to induce a strong proliferation of allogeneic CD4+ T cells. Th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.8.1177
更新日期:1994-08-01 00:00:00
abstract::Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood of C57BL/6 mice of various ages revealed that there was a reciprocal age-associated change in these two subpopulations,...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.1.97
更新日期:1995-01-01 00:00:00
abstract::The lectin complement pathway is initiated by binding of mannose-binding lectin (MBL) and MBL-associated serine protease (MASP) to carbohydrates. In the human lectin pathway, MASP-1 and MASP-2 are involved in the proteolysis of C4, C2 and C3. Here we report that the human MBL-MASP complex contains a new 22 kDa protein...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.859
更新日期:1999-05-01 00:00:00
abstract::It has previously been described that V gamma 3 cells can proliferate extensively in vitro in the presence of different cytokines. Here, the role of cytokines in the maintenance of V gamma 3 cells in the thymus has been determined. Culture of fetal thymocytes in cell suspension for 24 h showed that, whereas immature T...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.5.843
更新日期:1995-05-01 00:00:00