Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response

Yerkovich, Stephanie T.; Roponen, Marjut; Smith, Miranda; McKenna, Kathy; Bosco, Anthony; Subrata, Lily S.; Mamessier, Émilie; Wikström, Matthew E.; Souëf, P. Le; Sly, Peter D.; Holt, Patrick G.; Upham, John W.

doi:10.1016/j.jaci.2008.09.009

Cited by 65 publications

(72 citation statements)

References 51 publications

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“…In addition to coating the endothelium throughout all vascular beds, TM expression has been widely detected in several other tissues suggesting a multifunctionality beyond its widely established anticoagulation and anti-inflammatory roles (167). It has been identified in human gestational tissues such as placenta and myometrium (166), the gingival epithelium (100), keratinocytes (138), polymorphonuclear neutrophils (30), monocytes (164), dendritic cells (190), osteoblasts (94), and even platelets (153). TM has also been detected in a variety of cultured cells including smooth muscle cells (142), A549 small cell lung cancer cells (51) and NIH 3T3 cells (39), while soluble variants have been detected in human urine (108) and serum (194).…”

Section: Thrombomodulin Structurementioning

confidence: 99%

Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects

Martin

Murphy

Cummins

2013

American Journal of Physiology-Heart and Circulatory Physiology

173

163

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Section: Thrombomodulin Structurementioning

confidence: 99%

Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects

Martin

Murphy

Cummins

2013

American Journal of Physiology-Heart and Circulatory Physiology

173

163

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“…54 Finally, TM is expressed by monocytes and dendritic cells, and may therefore play a role in the pathogenesis of atopy and asthma. 55 In preclinical models, recombinant forms of TM confer protection against inflammation, ischemia-reperfusion injury, and endotoxemia. 51,53,[56][57][58] Sepsis-associated disseminated intravascular coagulation in patients responded beneficially to treatment with recombinant soluble TM, effects that may be attributed to its combined effects on inflammation and coagulation.…”

Section: The Protein C-thrombomodulin Mechanismmentioning

confidence: 99%

Coagulation and innate immune responses: can we view them separately?

Delvaeye

Conway

2009

Blood

261

210

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The horseshoe crab is often referred to as a "living fossil," representative of the oldest classes of arthropods, almost identical to species in existence more than 500 million years ago. Comparative analyses of the defense mechanisms used by the horseshoe crab that allowed it to survive mostly unchanged throughout the millennia reveal a common ancestry of the coagulation and innate immune systems that are totally integrated-indeed, almost inseparable. In human biology, we traditionally view the hemostatic pathways and those regulating innate immune responses to infections and tissue damage as entirely separate entities. But are they? The last couple of decades have revealed a remarkable degree of interplay between these systems, and the linking cellular and molecular mechanisms are rapidly being delineated. In this review, we present some of the major points of intersection between coagulation and innate immunity. We attempt to highlight the potential impact of these findings by identifying recently established paradigms that will hopefully result in the emergence of new strategies to treat a range of inflammatory and hemostatic disorders. IntroductionThe most menacing challenge to survival that is faced by organisms throughout the animal kingdom is invasion by infections and foreign antigens-events that are frequently accompanied by trauma or a wound. Organisms have thus necessarily developed a variety of effective means to restrict and to fight infections, to contain wounds by limiting bleeding with clot formation, and to rapidly initiate healing. The coexistence of thrombosis with inflammatory responses supports the notion that common molecular mechanisms regulate these complex biologic systems. The last couple of decades have seen major progress in identifying cellular and molecular links between these systems.In this review, we consider some of the key pathways involved in hemostasis, innate immunity, and inflammation, and provide recent data that demonstrate how they are integrated. The interactions are multiple and complex, and present new challenges to identify those that are clinically relevant, with the promise of discovering novel and more effective therapies for a range of diseases. CoagulationThe coagulation system is characterized by the sequential, rapid, and highly localized activation of a series of serine proteases, culminating in the generation of thrombin, with subsequent conversion of fibrinogen into a fibrin clot. Tissue factor (TF) is the key initiator of coagulation (reviewed in Mackman 1 ), and is expressed primarily by subendothelial mural cells and adventitial fibroblasts in and around the vessel wall. Somewhat controversial, it may also be expressed at low levels by monocytes and neutrophils, and found circulating in microparticles and in a soluble form. 2 With vascular endothelial cell damage, TF is exposed to the circulation, and complexes with factor VII/VIIa, initiating activation of factors IX and X. Factor Xa converts prothrombin to thrombin in sufficient quantities to activat...

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“…Froidure and colleagues recently reported that persistent asthma symptoms following a period of allergen avoidance was associated with the extent to which cDC were able to promote Th2 cytokine production by CD4 T-cells 26 . House dust mite allergen upregulates CD141 expression on monocyte derived DC 27 . This is significant because CD141 expressing DC induce a strongly Th2-polarized cytokine response in naïve 28 and memory CD4 T-cells 27 , while CD141 expression in blood leukocytes is elevated during acute asthma exacerbations 27 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…House dust mite allergen upregulates CD141 expression on monocyte derived DC 27 . This is significant because CD141 expressing DC induce a strongly Th2-polarized cytokine response in naïve 28 and memory CD4 T-cells 27 , while CD141 expression in blood leukocytes is elevated during acute asthma exacerbations 27 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%