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 cytokine VEGF-A in the cornea are associated with HSK severity. Here, we examined the impact of VEGF-A on neurologic changes that underly HSK using a mouse model of HSV-1 corneal infection. Both CD4+ T cells and myeloid cells produced pathogenic levels of VEGF-A within HSV-1-infected corneas, and CD4+ cell depletion promoted reinnervation of HSK corneas with sensory nerves. In vitro, VEGF-A from infected corneas repressed sensory nerve growth and promoted sympathetic nerve growth. Neutralizing VEGF-A in vivo using bevacizumab inhibited sympathetic innervation, promoted sensory nerve regeneration, and alleviated disease. Thus, VEGF-A can shape the sensory and sympathetic nerve landscape within the cornea, with implications for the treatment of blinding corneal disease.
journal_name
Immunityjournal_title
Immunityauthors
Yun H,Yee MB,Lathrop KL,Kinchington PR,Hendricks RL,St Leger AJdoi
10.1016/j.immuni.2020.10.013subject
Has Abstractpub_date
2020-11-17 00:00:00pages
1050-1062.e5issue
5eissn
1074-7613issn
1097-4180pii
S1074-7613(20)30454-4journal_volume
53pub_type
杂志文章相关文献
IMMUNITY文献大全abstract::Chronic viral infections remain a global health concern. The early events that facilitate viral persistence have been linked to the activity of the immunoregulatory cytokine IL-10. However, the mechanisms by which IL-10 facilitates the establishment of chronic infection are not fully understood. Herein, we demonstrate...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2018.01.006
更新日期:2018-02-20 00:00:00
abstract::CD40(-/-) mice succumbed to low-dose aerosol infection with M. tuberculosis due to deficient IL-12 production leading to impaired priming of IFN-gamma T cell responses. In contrast, CD40L(-/-) mice were resistant to M. tuberculosis. This asymmetry in outcome of infection between the two knockout strains is likely due ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(03)00324-8
更新日期:2003-12-01 00:00:00
abstract::Commensal microbiota confers a goldilocks state of alertness to pathogens, yet restrains deleterious inflammation. In this issue of Immunity, Geuking et al. (2011) demonstrate that a minimal bacterial community of the Schaedler flora establishes a balance between pro- and anti-inflammatory T cells in the gut. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2011.05.008
更新日期:2011-05-27 00:00:00
abstract::Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80499-9
更新日期:1996-11-01 00:00:00
abstract::To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80090-4
更新日期:1999-08-01 00:00:00
abstract::Dendritic cells (DCs) are the sentinels of the immune system, sensing a diverse array of pathogens to stimulate a robust and appropriate immune response. To initiate responses to highly disparate challenges, DCs have diversified into multiple phenotypically, anatomically, and functionally distinct cell types. As a res...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2020.05.005
更新日期:2020-06-16 00:00:00
abstract::TCR transgenic mice that express a peptide antigen in keratinocytes develop a lethal CD8 T cell-dependent autoimmune disease. We employed an adoptive transfer system to understand this disease and show that transfer of low numbers of naive CD8 T cells into peptide transgenic mice caused chronic skin disease. The antig...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2004.07.019
更新日期:2004-09-01 00:00:00
abstract::Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genita...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2016.12.013
更新日期:2017-01-17 00:00:00
abstract::Regulatory T (Treg) cells are essential for maintaining immune homeostasis. Although Foxp3 expression marks the commitment of progenitors to Treg cell lineage, how Treg cells are generated during lymphocyte development remains enigmatic. We report here that the c-Rel transcription factor controlled development of Treg...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2009.10.006
更新日期:2009-12-18 00:00:00
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::The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebra...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)00017-0
更新日期:2000-08-01 00:00:00
abstract::Blood, lymphoid tissues, and placenta contain diverse subpopulations of natural killer (NK) cells that possess distinct immune functions. Recent studies have shown that human and mouse gut-associated lymphoid tissues harbor a unique NK cell subset that specializes in production of interleukin (IL)-22. This cytokine pl...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2009.06.008
更新日期:2009-07-17 00:00:00
abstract::Foxp3(+) Treg cells express transcription factors normally expressed by specific T helper cells at sites of inflammation. In this issue of Immunity, Koch et al. (2012) and Hall et al. (2012) demonstrate that IFN-γ and IL-27 distinctly induces T-bet(+) Treg cells via STAT-1 transcription factor activation. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2012.09.004
更新日期:2012-09-21 00:00:00
abstract::CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplanta...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2017.11.003
更新日期:2017-12-19 00:00:00
abstract::A cDNA clone encoding the human homolog of rat Jagged1 was isolated from normal human marrow. Analyses of human stromal cell lines indicate that this gene, designated hJagged1, is expressed by marrow stromal cells typified by the cell line HS-27a, which supports the long-term maintenance of hematopoietic progenitor ce...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80457-4
更新日期:1998-01-01 00:00:00
abstract::Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(01)00246-1
更新日期:2001-12-01 00:00:00
abstract::The β common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmu...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2019.03.022
更新日期:2019-04-16 00:00:00
abstract::Tumor necrosis factor receptor (TNFR) superfamily members can induce a context-dependent apoptosis or cell activation. However, the mechanisms by which these opposing programs are selected remain unclear. We show that in T cells, TNFR2 (TNFRSF1B) signaling is dramatically affected by the intracellular mediator RIP, a ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80152-1
更新日期:1999-12-01 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::A major mechanism maintaining immune tolerance is the deletion of potentially autoreactive thymocytes by apoptosis during development in the thymus. Previous reports suggest that apoptosis is induced by high avidity signals transduced via the T cell receptor; however, the role of signals transduced by other cell surfa...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80275-7
更新日期:1996-12-01 00:00:00
abstract::Checkpoint-blocking antibodies can generate potent anti-tumor responses by encouraging the immune system to seek and destroy cancer cells. At this time, the United States Food and Drug Administration has approved three checkpoint-blocking antibodies in three disease indications, and additional approvals are expected t...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2016.04.023
更新日期:2016-05-17 00:00:00
abstract::Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2018.10.014
更新日期:2018-12-18 00:00:00
abstract::In this issue of Immunity, Chaudhry et al. (2011) and Huber et al. (2011) report that control of Th17 cell responses during colonic inflammation requires direct signaling by IL-10 in regulatory T cells and Th17 cells. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2011.04.004
更新日期:2011-04-22 00:00:00
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...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.06.009
更新日期:2011-08-26 00:00:00
abstract::As humans age, their T cell repertoire becomes dominated by cells exhibiting "memory" characteristics. In this issue of Immunity, Su et al. (2013) demonstrate that a large percentage of virus-specific CD4(+) T cells also exhibit a memory phenotype in unexposed adults. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2013.02.002
更新日期:2013-02-21 00:00:00
abstract::T helper 17 (Th17) cells play major roles in autoimmunity and bacterial infections, yet how T cell receptor (TCR) signaling affects Th17 cell differentiation is relatively unknown. We demonstrate that CD4(+) T cells lacking Itk, a tyrosine kinase required for full TCR-induced phospholipase C-gamma (PLC-gamma1) activat...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2009.07.009
更新日期:2009-10-16 00:00:00
abstract::Effector T cells are critical for clearance of pathogens from sites of infection. Like cytotoxic CD8(+) T cells, CD4(+) helper T cells have been shown to deliver effector molecules directionally toward the immunological synapse, suggesting that infected cells need to be engaged individually to receive effector signals...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2012.05.015
更新日期:2012-07-27 00:00:00
abstract::Antigen-presenting cells (APC) degrade proteins intracellularly to generate peptides, which are then bound by products of the major histocompatibility complex (MHC) and exposed on the surface of the APC for recognition by T cells. The supply of antigenic peptides and their association with MHC molecules requires the c...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/s1074-7613(00)80176-4
更新日期:2000-03-01 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::In this issue of Immunity, Curotto de Lafaille et al. (2008) show that adaptive T regulatory cells control airway inflammation and that it is when they are generated that determines whether they function during acute or chronic inflammation. ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2008.07.001
更新日期:2008-07-18 00:00:00