Abstract：
:Cyclophilin A (CypA/Ppia) is a peptidyl-prolyl isomerase (PPIase) that binds the immunosuppressive drug cyclosporine. The resulting complex blocks T cell function by inhibiting the calcium-dependent phosphatase calcineurin. To identify the native function of CypA, long suspected of regulating signal transduction, we generated mice lacking the Ppia gene. These animals develop allergic disease, with elevated IgE and tissue infiltration by mast cells and eosinophils, that is driven by CD4+ T helper type II (Th2) cytokines. Ppia(-/-) Th2 cells were hypersensitive to TCR stimulation, a phenotype consistent with increased activity of Itk, a Tec family tyrosine kinase crucial for Th2 responses. CypA bound Itk via the PPIase active site. Mutation of a conformationally heterogeneous proline in the SH2 domain of Itk disrupted interaction with CypA and specifically increased Th2 cytokine production from wild-type CD4+ T cells. Thus, CypA inhibits CD4+ T cell signal transduction in the absence of cyclosporine via a regulatory proline residue in Itk.
journal_name
Immunityjournal_title
Immunityauthors
Colgan J,Asmal M,Neagu M,Yu B,Schneidkraut J,Lee Y,Sokolskaja E,Andreotti A,Luban Jdoi
10.1016/j.immuni.2004.07.005keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
189-201issue
2eissn
1074-7613issn
1097-4180pii
S1074-7613(04)00192-Xjournal_volume
21pub_type
杂志文章相关文献
IMMUNITY文献大全abstract：:Precise intrathymic cell migration is important for thymocyte maturation and organ architecture. The orchestration of thymocyte trafficking, however, is not well understood at a molecular level. Here, we described highly regulated plexinD1 expression on CD4+CD8+ double positive (DP) thymocytes. PlexinD1 expression was...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2008.10.008
更新日期：2008-12-19 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1)-infected corneas can develop a blinding immunoinflammatory condition called herpes stromal keratitis (HSK), which involves the loss of corneal sensitivity due to retraction of sensory nerves and subsequent hyperinnervation with sympathetic nerves. Increased concentrations of the cyt...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2020.10.013
更新日期：2020-11-17 00:00:00
abstract：:Epithelial cells orchestrate pulmonary homeostasis and pathogen defense and play a crucial role in the initiation of allergic immune responses. Maintaining the balance between homeostasis and inappropriate immune activation and associated pathology is particularly complex at mucosal sites that are exposed to billions ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2015.10.012
更新日期：2015-11-17 00:00:00
abstract：:The heat shock (HS) response is a universal response activated after exposure to various stimuli. The major HS protein (HSP) is the 72 kDa HSP70 with strong homology in different eukaryotic species. We demonstrate that HS treatment of mice leads to a strong induction of HSP70 in several organs and confers significant ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(02)00310-2
更新日期：2002-05-01 00:00:00
abstract：:The interferon-producing plasmacytoid dendritic cells (pDCs) share common progenitors with antigen-presenting classical dendritic cells (cDCs), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of pDCs is actively maintained in the s...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2010.11.023
更新日期：2010-12-14 00:00:00
abstract：:Major Histocompatibility Complex (MHC) class II molecules, including Human Leukocyte Antigen (HLA)-DR, present peptide fragments from proteins degraded in the endocytic pathway. HLA-DR is targeted to late-endocytic structures named MHC class II-containing Compartments (MIIC), where it interacts with HLA-DM. This chape...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2005.01.006
更新日期：2005-02-01 00:00:00
abstract：:The first lineage commitment step of hematopoietic stem cells (HSC) results in separation into distinct lymphoid and myeloid differentiation pathways, reflected in the generation of common lymphoid and myeloid progenitors (CLP and CMP, respectively). In this report we present the first evidence for a nonredundant regu...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(02)00419-3
更新日期：2002-10-01 00:00:00
abstract：:After acute inflammation or infection, tissue-resident macrophages are replaced by inflammatory DCs and effector macrophages that arise from circulating monocytes. In this issue of Immunity, Goldszmid et al. (2012) demonstrate a central role for NK cell-derived IFN-γ in signaling and facilitating this transition. ...
journal_title：Immunity
pub_type： 评论,杂志文章
doi：10.1016/j.immuni.2012.06.007
更新日期：2012-06-29 00:00:00
abstract：:To examine the role of the TNF-R superfamily signaling protein TRAF2 in mature B cell development and NF-kappaB activation, conditionally TRAF2-deficient mice were produced. B cells lacking TRAF2 expression in these mice possessed a selective survival advantage, accumulated in the lymph nodes and splenic marginal zone...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2004.09.011
更新日期：2004-11-01 00:00:00
abstract：:The mitochondrial antiviral signaling protein (MAVS) mediates the activation of NFkappaB and IRFs and the induction of interferons in response to viral infection. In vitro studies have also suggested that MAVS is required for interferon induction by cytosolic DNA, but the in vivo evidence is lacking. By generating MAV...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2006.04.004
更新日期：2006-05-01 00:00:00
abstract：:Acute lung injury (ALI) remains a serious health issue with little improvement in our understanding of the pathophysiology and therapeutic approaches. We investigated the mechanism that lipopolysaccharide (LPS) induces early neutrophil recruitment to lungs and increases pulmonary vascular permeability during ALI. Intr...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2015.03.007
更新日期：2015-04-21 00:00:00
abstract：:The immunological synapse is characterized by the reorganization of membrane proteins at the immunological synapse. Active cytoskeletal mechanisms are involved in recruiting the TCR, accessory molecules, and the integrin LFA-1 to the contact area. Other molecules like CD43 are excluded from the contact area, but the m...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/s1074-7613(01)00237-0
更新日期：2001-11-01 00:00:00
abstract：:The mechanisms underpinning integration of instructions that program naive CD8+ T cells for effector and/or memory differentiation are not well understood. Herein, we demonstrate that interleukin-12 (IL-12) enhanced and sustained antigen and costimulatory molecule (B7.1)-induced mTOR kinase activity in naive CD8+ (OT-...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2009.10.010
更新日期：2010-01-29 00:00:00
abstract：:Genetic variation influences how the genome is interpreted in individuals and in mouse strains used to model immune responses. We developed approaches to utilize next-generation sequencing datasets to identify sequence variation in genes and enhancer elements in congenic and backcross mouse models. We defined genetic ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2019.05.006
更新日期：2019-07-16 00:00:00
abstract：:Antigenic peptides are translocated by the TAP peptide transporter from the cytosol into the endoplasmic reticulum (ER) for loading onto MHC class I molecules. Peptides that fail to bind need to be removed from the ER. Here we provide evidence that peptide export utilizes the Sec61p translocon as demonstrated by block...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(00)00013-3
更新日期：2000-07-01 00:00:00
abstract：:Natural hosts for simian immunodeficiency virus (SIV) can be, and are often naturally, infected with species-specific SIVs, but do not develop acquired immunodeficiency syndrome (AIDS). These natural hosts maintain high SIV viral loads, but avoid immunodeficiency. Elucidating the mechanisms that allow natural hosts to...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2010.06.004
更新日期：2010-06-25 00:00:00
abstract：:Stimulator of interferon genes (STING, also named MITA, MYPS, or ERIS) is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1). Here we found that the nucleotide-binding, leucine-rich-repeat-containing protein, NLRC3, reduced STING-dependent innate immune...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2014.01.010
更新日期：2014-03-20 00:00:00
abstract：:The structure of H-2Dd complexed with the HIV-derived peptide P18-I10 (RGPGRAFVTI) has been determined by X-ray crystallography at 2.4 A resolution. This MHC class I molecule has an unusual binding motif with four anchor residues in the peptide (G2, P3, R/K/H5, and I/L/F9 or 10). The cleft architecture of H-2Dd includ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(00)80602-0
更新日期：1998-08-01 00:00:00
abstract：:The c-Myb transcription factor is crucial during definitive hematopoiesis. However, the embryonic lethality of Myb traditional null mutations has precluded analysis of c-Myb function in lymphocytes. Using tissue-specific inactivation at the Myb locus, we demonstrate that loss of Myb causes a partial block during B cel...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2005.08.005
更新日期：2005-09-01 00:00:00
abstract：:Toll-like receptors (TLRs) are the archetypal pattern recognition receptors (PRRs) envisioned by as innate sensors of pathogen attack and host triggers of an adaptive immune response. Two recent papers (Choe et al., 2005; Bell et al., 2005) reveal the distinctive architecture of a TLR sensor domain and hint at how thi...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2005.09.008
更新日期：2005-10-01 00:00:00
abstract：:To understand how orally introduced antigen regulates peripheral immune responses, we fed cytochrome c protein to mice transgenic for the beta chain of a cytochrome c-specific TCR and followed the antigen-specific T cell responses with a cyt c/I-Ek tetramer staining reagent. We find that within 6 hr of cytochrome c ad...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(00)80571-3
更新日期：1998-06-01 00:00:00
abstract：:Co-evolution with their bacterial hosts has led to viral countermeasures against CRISPR-mediated immunity. In a recent issue of Cell, Landsberger et al. (2018) and Borges et al. (2018) report that cooperation among bacteriophages and multiple infection events are necessary to overcome CRISPR immune responses. ...
journal_title：Immunity
pub_type： 评论,杂志文章
doi：10.1016/j.immuni.2018.08.023
更新日期：2018-09-18 00:00:00
abstract：:How is the amoeboid movement of lymphocytes in secondary lymphoid organs orchestrated? In this issue of Immunity, Bajénoff et al. (2006) demonstrate that stromal cell networks serve as guidance structures that direct and limit the migration of B and T cells in lymph nodes. ...
journal_title：Immunity
pub_type： 评论,杂志文章,评审
doi：10.1016/j.immuni.2006.11.002
更新日期：2006-12-01 00:00:00
abstract：:T cell activation induces functional changes in cell shape and cytoskeletal architecture. To facilitate the collection of dynamic, high-resolution images of activated T cells, we plated T cells on coverslips coated with antibodies to the T cell receptor (TCR). Using these images, we were able to quantitate the morphol...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(01)00112-1
更新日期：2001-03-01 00:00:00
abstract：:Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the light chain chain gene loci form functional immunoglobulin genes during B cell development. In mouse bone marrow the differential surface expression of B220 (CD45R), c-kit, CD25, and surrogate light chain as well as the cell cycle status ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/1074-7613(95)90131-0
更新日期：1995-11-01 00:00:00
abstract：:Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral ...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2018.12.027
更新日期：2019-01-15 00:00:00
abstract：:Although cellular receptors for immunoglobulins were first identified nearly 40 years ago, their central role in the immune response was discovered only in the last decade. They are key players in both the afferent and efferent phase of an immune response, setting thresholds for B cell activation, regulating the matur...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2005.11.010
更新日期：2006-01-01 00:00:00
abstract：:Galactocerebrosides (GCs) represent a major class of glycolipids in the nervous system. Here, we show that mice lacking the key enzyme to generate GCs, UDP-galactose:ceramide galactosyltransferase (CGT(-/-)), exhibit severe postnatal atrophy of all lymphoid organs, owing to a maturational arrest before the pro-B/T cel...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(03)00150-x
更新日期：2003-06-01 00:00:00
abstract：:The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-gamma production by TH1 effector cells. Here, we show that the expression of GADD45gamma is induced during T cell activation and that the level of expression is higher in TH1 cel...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(01)00141-8
更新日期：2001-05-01 00:00:00
abstract：:HLA-DM (DM) is a nonclassical MHC class II molecule that interacts with classical MHC II molecules in acidic compartments. During this association DM is supposed to catalyze the release of invariant chain (Ii)-derived CLIP peptides, as well as other peptides bound with low kinetic stability. Here we provide evidence t...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(00)80332-5
更新日期：1997-03-01 00:00:00
