Abstract:
:Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation. Importantly, a positive feedback loop involving autocrine LIF, LIFR, and STAT4 drove sustained IL-6 transcription. Besides IL-6, this autorine loop also drove the production of other key inflammatory factors including IL-8, granulocyte-colony stimulating factor (G-CSF), IL-33, IL-11, IL-1α, and IL-1β. These findings define the transcriptional regulation of fibroblast-mediated inflammation as distinct from leukocytes.
journal_name
Immunityjournal_title
Immunityauthors
Nguyen HN,Noss EH,Mizoguchi F,Huppertz C,Wei KS,Watts GFM,Brenner MBdoi
10.1016/j.immuni.2017.01.004subject
Has Abstractpub_date
2017-02-21 00:00:00pages
220-232issue
2eissn
1074-7613issn
1097-4180pii
S1074-7613(17)30026-2journal_volume
46pub_type
杂志文章相关文献
IMMUNITY文献大全abstract::Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2013.12.004
更新日期:2014-01-16 00:00:00
abstract::The development of human innate lymphoid cells (ILCs) remains poorly characterized. In a recent issue of Cell, Lim et al. show that human peripheral-blood CD117+ ILCs harbor ILC precursors (ILCPs) derived from hematopoietic stem cells. Peripheral-blood ILCPs can generate all ILC subsets in vivo and in vitro. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2017.03.002
更新日期:2017-03-21 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 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::For a brief period during fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules surprisingly express the Peyer's patch addressin MAdCAM-1. This expression allows initial seeding of this incipient structure by two unusual lymphocyte populations selectively expressing the Peyer's patc...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80371-4
更新日期:1997-10-01 00:00:00
abstract::Minor or histocompatibility (H) antigens are recognized by CD4+ and CD8+ T lymphocytes as short polymorphic peptides associated with MHC molecules. They are the targets of graft versus host and graft versus leukemia responses following bone marrow transplantation between HLA-identical siblings. Several genes encoding ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80221-6
更新日期:2000-06-01 00:00:00
abstract::Among 631 substitutions present in 90 nurse shark immunoglobulin light chain somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence of mutations in perinatal sequences and the bias for one mutating V gene in adults suggest that the diversification is antigen dependent. The substitutions share...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(02)00300-x
更新日期:2002-04-01 00:00:00
abstract::Inflammasomes are supramolecular organizing centers that operate to drive interleukin-1 (IL-1)-dependent inflammation. Depending on context, inflammatory caspases act upstream or downstream of inflammasome assembly, serving as the principal enzymes that control activities of these organelles. In this review, we discus...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2019.08.005
更新日期:2019-10-15 00:00:00
abstract::Human cytomegalovirus (HCMV) can suppress and evade the immune system. We have identified as a mechanism the ability of HCMV to infect dendritic cells (DC), which initiate the antiviral immune response. HCMV-infected DC show enhanced expression of costimulatory molecules. In contrast, MHC molecules are partially downr...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(01)00239-4
更新日期:2001-12-01 00:00:00
abstract::Interleukin-1 (IL-1) receptor signaling is necessary for control of Mycobacterium tuberculosis (Mtb) infection, yet the role of its two ligands, IL-1α and IL-1β, and their regulation in vivo are poorly understood. Here, we showed that both IL-1α and IL-1β are critically required for host resistance and identified two ...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.12.002
更新日期:2011-12-23 00:00:00
abstract::Numerous regulatory programs have been identified that contribute to the restoration of homeostasis at the conclusion of immune responses and to safeguarding against the detrimental effects of chronic inflammation and autoimmune pathology. Malignant cells may usurp these pathways to create immunosuppressive networks t...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2012.03.004
更新日期:2012-03-23 00:00:00
abstract::T cell receptor (TCR)-mediated cytoskeletal reorganization is considered to be actin-related protein (Arp) 2/3 complex dependent. We therefore examined the requirement for Arp2/3- and formin-dependent F-actin nucleation during T cell activation. We demonstrated that without Arp2/3-mediated actin nucleation, stimulated...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2007.01.008
更新日期:2007-02-01 00:00:00
abstract::Aging results in increased myelopoiesis, which is linked to the increased incidence of myeloid leukemias and production of myeloid-derived suppressor cells. Here, we examined the contribution of plasma cells (PCs) to age-related increases in myelopoiesis, as PCs exhibit immune regulatory function and sequester in bone...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2019.06.006
更新日期:2019-08-20 00:00:00
abstract::In this issue of Immunity, Nagashima et al., Wallrapp et al., and Xu et al. demonstrate that the neuropeptide calcitonin gene-related peptide (CGRP) fine tunes type 2 innate immune response via suppressing group 2 innate lymphoid cells (ILC2s). ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2019.09.015
更新日期:2019-10-15 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::Curing HIV infection has been impossible, with the exception of the "Berlin Patient." Martinez-Navio et al. (2019) in Miami herein present a rare monkey whose virus was controlled for >3 years after a single genetic intervention that led to persistent production of HIV-neutralizing antibodies in vivo. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2019.02.010
更新日期:2019-03-19 00:00:00
abstract::Interleukin-22 (IL-22) plays a critical role in mucosal defense, although the molecular mechanisms that ensure IL-22 tissue distribution remain poorly understood. We show that the CXCL16-CXCR6 chemokine-chemokine receptor axis regulated group 3 innate lymphoid cell (ILC3) diversity and function. CXCL16 was constitutiv...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2014.10.007
更新日期:2014-11-20 00:00:00
abstract::Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rollin...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2014.03.004
更新日期:2014-04-17 00:00:00
abstract::Regulatory T cell-mediated dominant tolerance has been demonstrated to play an important role in the prevention of autoimmunity. Here, we present data arguing that the forkhead transcription factor Foxp3 acts as the regulatory T cell lineage specification factor and mediator of the genetic mechanism of dominant tolera...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2005.01.016
更新日期:2005-03-01 00:00:00
abstract::Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Treg cells can respond to low IL-2 levels, but the mechanisms of STAT5 activation during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Ms...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2018.10.010
更新日期:2018-11-20 00:00:00
abstract::HIV-infected humans and SIV-infected rhesus macaques who remain healthy despite long-term infection exhibit exceptionally low levels of virus replication and active antiviral cellular immune responses. In contrast, sooty mangabey monkeys that represent natural hosts for SIV infection do not develop AIDS despite high l...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(03)00060-8
更新日期:2003-03-01 00:00:00
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 g...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2004.07.005
更新日期:2004-08-01 00:00:00
abstract::Differentiation of naive T cells into mature Th2 cells is associated with the appearance of a complex pattern of DNase I hypersensitive (DH) sites within the IL-4/IL-13 cytokine gene cluster. We show here that targeted deletion of an inducible DH site, V(A), and the adjacent conserved DH site V (CNS-2) selectively com...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(02)00334-5
更新日期:2002-07-01 00:00:00
abstract::The emerging notion of environment-induced reprogramming of Foxp3(+) regulatory T (Treg) cells into helper T (Th) cells remains controversial. By genetic fate mapping or adoptive transfers, we have identified a minor population of nonregulatory Foxp3(+) T cells exhibiting promiscuous and transient Foxp3 expression, wh...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/j.immuni.2011.12.012
更新日期:2012-02-24 00:00:00
abstract::We have identified RORgamma t, a novel, thymus-specific isoform of the orphan nuclear receptor RORgamma that is expressed predominantly in CD4+ CD8+ double-positive thymocytes. Ectopic expression of RORgamma t protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Fas ligand. F...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80645-7
更新日期:1998-12-01 00:00:00
abstract::Invariant chain (Ii)-negative mice exhibit defects in MHC class II assembly and transport that results in reduced levels of surface class II, altered antigen presentation, and inefficient positive selection of CD4+ T cells. Many CD4+ T cells that do mature in Ii-negative mice express a cell surface phenotype consisten...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/1074-7613(95)90120-5
更新日期:1995-09-01 00:00:00
abstract::In this issue of Immunity, Schweighoffer et al. (2013) report that full BAFF responsiveness in B cells requires the tyrosine kinase Syk and that BAFF may co-opt components of the B cell receptor in transmitting its survival signal. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2013.03.001
更新日期:2013-03-21 00:00:00
abstract::Regulatory B (Breg) cells are immunosuppressive cells that support immunological tolerance. Through the production of interleukin-10 (IL-10), IL-35, and transforming growth factor β (TGF-β), Breg cells suppress immunopathology by prohibiting the expansion of pathogenic T cells and other pro-inflammatory lymphocytes. R...
journal_title:Immunity
pub_type: 杂志文章,评审
doi:10.1016/j.immuni.2015.04.005
更新日期:2015-04-21 00:00:00
abstract::In this issue of Immunity, Mrdjen et al. (2018) use high-dimensional single-cell proteomics and high parametric mass cytometry to provide insight into the long-lasting issue of how to identify and characterize both resident and recruited leukocyte populations in healthy, aged, and diseased CNS. ...
journal_title:Immunity
pub_type: 评论,杂志文章
doi:10.1016/j.immuni.2018.02.009
更新日期:2018-02-20 00:00:00
abstract::C57BI/6 mice infected with mouse hepatitis virus, strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis. Infectious virus can be isolated only from symptomatic mice. In C57BI/6 mice, two CD8+ T cell epitopes within the MHV-JHM surface glycoprotein were previously identified. Here, we show that mutatio...
journal_title:Immunity
pub_type: 杂志文章
doi:10.1016/s1074-7613(00)80320-9
更新日期:1996-09-01 00:00:00