Abstract:
:Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf-like GTPase Arl8b as a critical regulator of cargo delivery to lysosomes. Homotypic fusion and vacuole protein sorting (HOPS) complex members were identified as effectors of Arl8b and were dependent on Arl8b for recruitment to lysosomes, suggesting that Arl8b-HOPS plays a general role in directing traffic to lysosomes. Moreover, the formation of CD1 antigen-presenting complexes in lysosomes, their delivery to the plasma membrane, and phagosome-lysosome fusion were all markedly impaired in Arl8b silenced cells resulting in corresponding defects in T cell activation and microbial killing. Together, these results define Arl8b as a key regulator of lysosomal cellular and immunological functions.
journal_name
Immunityjournal_title
Immunityauthors
Garg S,Sharma M,Ung C,Tuli A,Barral DC,Hava DL,Veerapen N,Besra GS,Hacohen N,Brenner MBdoi
10.1016/j.immuni.2011.06.009subject
Has Abstractpub_date
2011-08-26 00:00:00pages
182-93issue
2eissn
1074-7613issn
1097-4180pii
S1074-7613(11)00267-6journal_volume
35pub_type
杂志文章相关文献
IMMUNITY文献大全abstract::The stromal scaffold of the lymph node (LN) paracortex is built by fibroblastic reticular cells (FRCs). Conditional ablation of lymphotoxin-β receptor (LTβR) expression in LN FRCs and their mesenchymal progenitors in developing LNs revealed that LTβR-signaling in these cells was not essential for the formation of LNs....
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2013.03.012
更新日期:2013-05-23 00:00:00
abstract::In this issue of Immunity, Conche et al. (2009) define an antigen-independent signaling pathway that is dependent on cyclic adenosine monophosphate and extracellular signal-regulated kinase and T cells for subsequent T cell antigen receptor signaling. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2008.12.007
更新日期:2009-01-16 00:00:00
abstract::Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6loCD69hi expressing a transcription factor IRF4 and higher-affinit...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2018.03.027
更新日期:2018-04-17 00:00:00
abstract::Monobenzone is a pro-hapten that is exclusively metabolized by melanocytes, thereby haptenizing melanocyte-specific antigens, which results in cytotoxic autoimmunity specifically against pigmented cells. Studying monobenzone in a setting of contact hypersensitivity (CHS), we observed that monobenzone induced a long-la...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.05.008
更新日期:2016-06-21 00:00:00
abstract::The participation of a specific subset of B cells and how they are regulated in cancer is unclear. Here, we demonstrate that the proportion of CD5(+) relative to interleukin-6 receptor α (IL-6Rα)-expressing B cells was greatly increased in tumors. CD5(+) B cells responded to IL-6 in the absence of IL-6Rα. IL-6 directl...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.04.003
更新日期:2016-04-19 00:00:00
abstract::Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into devel...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80142-9
更新日期:1999-12-01 00:00:00
abstract::Cytokine regulation of B cell development was analyzed using interleukin-2 (IL-2)-induced transcription of the J chain gene as a model system. A nuclear target of the IL-2 signal was identified as the Pax5 transcription factor, BSAP, which recognizes a negative regulatory motif in the J chain promoter. Functional assa...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80263-0
更新日期:1996-10-01 00:00:00
abstract::The products of V(D)J recombination are coding and signal joints. We show that the nucleotide composition of the coding ends affects V(D)J recombination. The presence of Ts at the 5' end of either the 12 mer or the 23 mer recombination signal sequence (RSS) greatly decreases coding and signal joint formation, and Ts a...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90146-9
更新日期:1995-04-01 00:00:00
abstract::Transcriptional regulation of the Nos2 gene encoding inducible nitric oxide synthase (iNOS) requires type I interferon (IFN-I) signaling and additional signals emanating from pattern recognition receptors. Here we showed sequential and cooperative contributions of the transcription factors ISGF3 (a complex containing ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2010.07.001
更新日期:2010-07-23 00:00:00
abstract::The elongated complementary-determining region (CDR) 3beta found in the unliganded KB5-C20 TCR protrudes from the antigen binding site and prevents its docking onto the peptide/MHC (pMHC) surface according to a canonical diagonal orientation. We now present the crystal structure of a complex involving the KB5-C20 TCR ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(02)00288-1
更新日期:2002-03-01 00:00:00
abstract::Despite compromised T cell antigen receptor (TCR) signaling, mice in which tyrosine 136 of the adaptor linker for activation of T cells (LAT) was constitutively mutated (Lat(Y136F) mice) accumulate CD4(+) T cells that trigger autoimmunity and inflammation. Here we show that equipping postthymic CD4(+) T cells with LAT...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2009.05.013
更新日期:2009-08-21 00:00:00
abstract::Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca(2+) mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk(-/-) and Rlk(-/-)Itk(-/-) mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless,...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2006.05.011
更新日期:2006-07-01 00:00:00
abstract::The chemokine sink hypothesis pertaining to erythrocyte Duffy Antigen Receptor for Chemokines (DARC) during inflammation has received considerable attention, but lacks direct in vivo evidence. Here we demonstrate, using mice with a targeted deletion in CXCL5, that CXCL5 bound erythrocyte DARC and impaired its chemokin...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2010.07.009
更新日期:2010-07-23 00:00:00
abstract::During signal transduction through the B cell antigen receptor (BCR), several signaling elements are brought together by the adaptor protein SLP-65. We have investigated the role of SLP-65 in B cell maturation and function in mice deficient for SLP-65. While the mice are viable, B cell development is affected at sever...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80130-2
更新日期:1999-11-01 00:00:00
abstract::Reciprocal interactions between the metabolic system and immune cells play pivotal roles in diverse inflammatory diseases, but the underlying mechanisms remain elusive. The activation of bile acid-mediated signaling has been linked to improvement in metabolic syndromes and enhanced control of inflammation. Here, we de...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.09.008
更新日期:2016-10-18 00:00:00
abstract::We have generated a site-directed transgenic (sd-tg) mouse model in which the JH locus has been replaced with a rearranged VDJ coding for the heavy chain of an anti-DNA antibody. In these mice, B cells expressing the anti-dsDNA specificity are negatively regulated. We observe a novel mechanism for B cell tolerance, re...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90064-0
更新日期:1995-12-01 00:00:00
abstract::In 2006, a clinical trial with the CD28 superagonistic antibody TGN1412 in London turned into a catastrophe. Studies are beginning to unravel the difference between the human and preclinical animal response to the antibody. ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2008.04.003
更新日期:2008-05-01 00:00:00
abstract::As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to imm...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2020.07.020
更新日期:2020-09-15 00:00:00
abstract::MicroRNA (miRNA)-deficient helper T cells exhibit abnormal IFN-γ production and decreased proliferation. However, the contributions of individual miRNAs to this phenotype remain poorly understood. We conducted a screen for miRNA function in primary T cells and identified individual miRNAs that rescue the defects assoc...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.07.009
更新日期:2011-08-26 00:00:00
abstract::Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2013.10.019
更新日期:2013-12-12 00:00:00
abstract::De Libero et al. (2005) demonstrate in this issue of Immunity that bacterial infection leads to increased synthesis of autologous glycolipids that are recognized by CD1-restricted human T cells, indicating that recognition of inducible self-glycolipids could be a mechanism for microbial detection. This mechanism also ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2005.06.001
更新日期:2005-06-01 00:00:00
abstract::The expression of KIR and CD94:NKG2 receptors was determined for more than 100 natural killer (NK) cell clones obtained from two blood donors who differ in their HLA class I and KIR genes. More than 98% of the clones were inhibited by individual autologous class I allotypes, and every clone was inhibited by the combin...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80393-3
更新日期:1997-12-01 00:00:00
abstract::To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo, we inactivated csk in granulocytes by conditional mutagenesis (Cre/loxP). Mutant mice (Csk-GEcre) developed acute multifocal inflammation in skin and lung. Animals were protected from...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(04)00023-8
更新日期:2004-02-01 00:00:00
abstract::The transcriptional repressor Blimp-1 is considered the master regulator of plasma-cell differentiation. In this issue of Immunity, Kallies et al. (2007) identify a Blimp-1-independent stage of differentiation, followed by Blimp-1-dependent terminal differentiation. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2007.05.005
更新日期:2007-05-01 00:00:00
abstract::The investigation of gammadelta T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downs...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2009.08.006
更新日期:2009-08-21 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::V(H)-DJ(H) recombination of the immunoglobulin heavy chain (Igh) locus is temporally and spatially controlled during early B cell development, and yet no regulatory elements other than the V(H) gene promoters have been identified throughout the entire V(H) gene cluster. Here, we discovered regulatory sequences that ar...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.02.005
更新日期:2011-02-25 00:00:00
abstract::T cells that produce IL-17 (T helper 17 cells) are implicated in autoimmune pathogenesis. In this issue of Immunity, Yang et al. (2008) report that the closely related orphan nuclear receptors ROR alpha and ROR gamma t work together to regulate T helper (Th)17 cell differentiation. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2007.12.006
更新日期:2008-01-01 00:00:00
abstract::In this issue of Immunity, Silver et al. (2012) provide evidence that murine Toll-like receptor 9 (TLR9) expression and function in innate and adaptive immunity is controlled by the circadian cycle. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2012.02.003
更新日期:2012-02-24 00:00:00
abstract::Memory B cells (MBCs) and plasma cells (PCs) constitute the two cellular outputs of germinal center (GC) responses that together facilitate long-term humoral immunity. Although expression of the transcription factor BLIMP-1 identifies cells undergoing PC differentiation, no such marker exists for cells committed to th...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2017.11.022
更新日期:2017-12-19 00:00:00