Seminars in immunology
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Seminars in immunology · Jun 2018
ReviewThe critical role of C5a as an initiator of neutrophil-mediated autoimmune inflammation of the joint and skin.
The deposition of IgG autoantibodies in peripheral tissues and the subsequent activation of the complement system, which leads to the accumulation of the anaphylatoxin C5a in these tissues, is a common hallmark of diverse autoimmune diseases, including rheumatoid arthritis (RA) and pemphigoid diseases (PDs). C5a is a potent chemoattractant for granulocytes and mice deficient in its precursor C5 or its receptor C5aR1 are resistant to granulocyte recruitment and, consequently, to tissue inflammation in several models of autoimmune diseases. However, the mechanism whereby C5a/C5aR regulates granulocyte recruitment in these diseases has remained elusive. ⋯ The latter, subsequently, initiates by autocrine/paracrine actions via its receptor BLT1 the egress of neutrophils from the blood vessel lumen into the interstitial. Compelling evidence suggests that this C5a/C5aR1-LTB4/BLT1 axis driving granulocyte recruitment in arthritis may represent a more generalizable biological principle critically regulating effector cell recruitment in other IgG autoantibody-induced diseases, such as in pemphigoid diseases. Thus, dual inhibition of C5a and LTB4, as implemented in nature by the lipocalin coversin in the soft-tick Ornithodoros moubata, may constitute a most effective therapeutic principle for the treatment of IgG autoantibody-driven diseases.
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Seminars in immunology · Apr 2017
ReviewDifferences and similarities between sublingual immunotherapy of allergy and oral tolerance.
Allergen immunotherapy is the only treatment altering the natural course of IgE-mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has been historically considered as a reference, we discuss herein the relative advantages of the sublingual and oral routes as alternatives to SCIT in order to elicit allergen-specific tolerance. ⋯ While still exploratory, oral immunotherapy (OIT) has shown promising results in the desensitization of patients with food allergies. We review at both biological and clinical levels the perspectives currently pursued for those two mucosal routes.
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Seminars in immunology · Dec 2016
ReviewRole of platelets in neutrophil extracellular trap (NET) production and tissue injury.
In addition to their well-known role as the cellular mediator of thrombosis, numerous studies have identified key roles for platelets during various disease processes. Importantly, platelets play a critical role in the host immune response, directly interacting with, and eliminating pathogens, from the blood stream. In addition to pathogen clearance, platelets also contribute to leukocyte recruitment at sites of infection and inflammation, and modulate leukocyte activity. ⋯ Additionally, NET components have been suggested to be key activators of infection-induced coagulopathy. These critical roles, at the interface between hemostasis and immunity, highlight the need for balance in the platelet response; too little platelet activity results in bleeding and immune deficit, too much leads to tissue pathogenesis. In this review, we highlight recent advances in our understanding of the role platelets play in inflammation, the link between platelets and NETs and the role platelets play in disease pathogenesis.
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Seminars in immunology · Dec 2016
ReviewBlood coagulation in immunothrombosis-At the frontline of intravascular immunity.
While hemostasis is the physiological process that prevents blood loss after vessel injury, thrombosis is often portrayed as a pathologic event involving blood coagulation and platelet aggregation eventually leading to vascular occlusion and tissue damage. However, recent work suggests that thrombosis can also be a physiological process, termed immunothrombosis, initiated by the innate immune system providing a first line of defense to locally control infection. Fibrin forms the structural basis of immunothrombotic clots and its assembly involves the concerted action of coagulation factors, platelets and leukocytes. Here, we summarize the cellular and molecular events that initiate fibrin formation during the innate immune response and discuss how aberrant activation of these pathways fosters pathologies associated with thrombosis, including disseminated intravascular coagulation and atherothrombosis.
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Seminars in immunology · May 2015
ReviewThe resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution.
Studies into the mechanisms in resolution of self-limited inflammation and acute reperfusion injury have uncovered a new genus of pro-resolving lipid mediators coined specialized pro-resolving mediators (SPM) including lipoxins, resolvins, protectins and maresins that are each temporally produced by resolving-exudates with distinct actions for return to homeostasis. SPM evoke potent anti-inflammatory and novel pro-resolving mechanisms as well as enhance microbial clearance. While born in inflammation-resolution, SPM are conserved structures with functions discovered in microbial defense, pain, organ protection and tissue regeneration, wound healing, cancer, reproduction, and neurobiology-cognition. This review covers these SPM mechanisms and other new omega-3 PUFA pathways that open their path for functions in resolution physiology.