Toll in the vessel wall—for better or worse?

Hansson, Göran K.; Lundberg, Anna M.

doi:10.1073/pnas.1019722108

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Under conditions of tolerance breakdown, identification of the triggers of lymphocyte activation, their emigration from SLOs or TLOs, and mechanisms of lymphocyte homing to attack the antigen-specific targets in human disease remain important issues of autoimmune disease research including atherosclerosis (Hansson et al, 1989 ; Lang et al, 2005 ; Galkina and Ley, 2009 ; Hermansson et al, 2010 ; Hansson and Lundberg, 2011 ). Indeed, TLOs are closely associated with various autoimmune diseases but their presence does not seem to be sufficient to trigger organ injury.…”

Section: Tlos Arise In Chronic Non-resolving Inflammation Of Periphermentioning

confidence: 99%

“…A major function of TLOs is to organize B cell immunity: B cells reside, act, proliferate, and undergo affinity maturation locally using the inflammatory survival niches and lymphorganogenic chemokines such as CXCL13, CCL21, and lymphotoxin (Schroder et al, 1996 ; Luster, 1998 ; Stott et al, 1998 ; Kim et al, 1999 ; Gräbner et al, 2009 ; Sweet et al, 2011 ). Thus, the initiation of autoimmune disease is the result of a multistep process in which TLO neogenesis appears to be required but is not sufficient: Additional events including toll-like receptor activation and breakdown of tissue barriers such as the blood brain barrier in multiple sclerosis (see below) are needed to trigger overt autoimmune disease (Cole et al, 2011 ; Hansson and Lundberg, 2011 ). To facilitate local adaptive immune responses, TLOs generate and assemble conduits, HEVs, and lymph vessels to boost T and B cell recruitment and to promote their movement within T cell areas or B cell follicles as shown for ATLOs.…”

Section: Tlos Arise In Chronic Non-resolving Inflammation Of Periphermentioning

confidence: 99%

See 1 more Smart Citation

Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

Weih¹,

Gräbner²,

Hu³

et al. 2012

Front. Physio.

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Tertiary lymphoid organs (TLOs) emerge in tissues in response to non-resolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs) in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE−/− mice. ATLOs are structured into T cell areas harboring conventional dendritic cells and monocyte-derived DCs; B cell follicles containing follicular dendritic cells within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV) neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory (nTregs; iTregs) cells as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses toward atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease.

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Section: Tlos Arise In Chronic Non-resolving Inflammation Of Periphermentioning

confidence: 99%

Section: Tlos Arise In Chronic Non-resolving Inflammation Of Periphermentioning

confidence: 99%

Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

Weih¹,

Gräbner²,

Hu³

et al. 2012

Front. Physio.

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“…17 TLRs recognize conserved molecular signatures on microorganisms called pathogen-associated molecular patterns and rapidly alert the host to potential dangers. 15 Apart from their role in host defense mechanisms, TLRs 1, 2, 3, 4, 6, 7, and 9 have critical functions in pathologies like diabetes, 18,19 cancer, 20,21 cardiovascular diseases, 22,23 kidney diseases, 24,25 gastrointestinal diseases, 26,27 endocrine dysfuntionalities, 28 and CNS diseases. 29,30 In the present study, we identified TLR2 as one of the crucial TLRs that mediates the protumorigenic effect of microglia on glioma growth and expansion.…”

mentioning

confidence: 99%

Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion

Vinnakota

Hu²,

Ku³

et al. 2013

Neuro-Oncology

122

143

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“…In fact, we have recently found that diabetic-associated augmented vascular contractile responses are partially mediated by TLR2 [38]. TLR2 and TLR4 with respect to vascular contraction have recently emerged as a novel signaling receptors, a role for TLR3 in the vasculature remains less explored [20], and current studies to identify both protective and harmful effects of TLR3 activation are needed. For example, using TLR3-deficient mice, Cole et al [14] found that TLR3 has a protective impact on the vascular wall after mechanical and hypercholesterolemia-induced arterial injury.…”

Section: Discussionmentioning

confidence: 97%

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

Hardigan

Spitler

Matsumoto³

et al. 2015

Pflugers Arch - Eur J Physiol

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Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

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Toll in the vessel wall—for better or worse?

Cited by 6 publications

References 17 publications

Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

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