Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

Randolph, Gwendalyn J.; Bala, Shashi; Rahier, Jean–François; Johnson, Michael W.; Wang, Peter L.; Nalbantoglu, ILKe; Dubuquoy, Laurent; Chau, Amélie; Pariente, Benjamin; Kartheuser, Alex; Zinselmeyer, Bernd H.; Colombel, Jean–Frédéric

doi:10.1016/j.ajpath.2016.07.026

Cited by 78 publications

(58 citation statements)

References 21 publications

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“…Thus, chemotaxis to the lymphatic vessel is essential. DCs are the best-studied cell type in this regard, and it is well established that a particularly relevant chemokine-receptor pairing is CCL21, expressed by the lymphatic vessels (40) (Table 1), attracting DCs that express the CCL21 receptor CCR7 (41–43). CCR7 was initially reported to be necessary for T cell entry into lymphatics from skin (44), but further studies found that it was not required (45).…”

Section: Structure and Properties Of The Lymphatic Systemmentioning

confidence: 99%

“…These all independently intersect with, and drain into, contractile lymphatic collecting vessels that originate at the mesenteric border and run antiparallel to the intestinal wall through mesenteric fat until they reach mesenteric lymph nodes (74). In humans, there is a fourth lymphatic capillary bed that is located in the mesenteric fat itself, mostly localized just beneath the serosal epithelial covering of the mesenteric adipose tissue (43). These four lymphatic capillary networks carry many critical antigens to draining lymph nodes, and the villus lacteals also transport dietary fat that is packaged into chylomicrons (8).…”

Section: Lymphatic Collecting Vessel Permeability and Integrity As Rementioning

confidence: 99%

“…When, during surgical resection of Crohn’s disease–affected ileum, dyes are injected into the mucosa to drain out through mesenteric collecting vessels, embedded in mesenteric adipose tissue, the dye front is often deviated and follows the nascent frontier of the expanding creeping fat (43). This relationship caused us to wonder if significant remodeling of the fat-localized mesenteric collecting vessels occurred.…”

Section: Lymphatic Collecting Vessel Permeability and Integrity As Rementioning

confidence: 99%

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The Lymphatic System: Integral Roles in Immunity

Randolph

Ivanov

Zinselmeyer

et al. 2017

Annu. Rev. Immunol.

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258

255

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The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment. We cover these topics herein and discuss how other properties of the lymphatic vasculature, such as mechanisms of lymphatic contraction (which immunologists traditionally do not take into account), are nonetheless integral in the immune system. Much is yet unknown, and this nascent subject is ripe for exploration. We argue that to consider the impact of lymphatic biology in any given immunological interaction is a key step toward integrating immunology with organ physiology and ultimately many complex pathologies.

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Section: Structure and Properties Of The Lymphatic Systemmentioning

confidence: 99%

Section: Lymphatic Collecting Vessel Permeability and Integrity As Rementioning

confidence: 99%

Section: Lymphatic Collecting Vessel Permeability and Integrity As Rementioning

confidence: 99%

See 1 more Smart Citation

The Lymphatic System: Integral Roles in Immunity

Randolph

Ivanov

Zinselmeyer

et al. 2017

Annu. Rev. Immunol.

Self Cite

258

255

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show abstract

“…73 It appears to be unlikely that IAL improves lymphatic drainage function under these conditions that manifest with rampant edema and failure of dendritic cells to migrate from the tissue, 77 but this may be partially caused by downstream reductions in pumping or lymphatic obstructions with lymphangitis. 73,78 In Crohn's mesenteric tissue biopsies, granulomatous lymphangitis further propagates inflammation as CD20þ B-cell rich TLOs reside along the mesenteric lymphatic vessels inhibiting flow and likely modulating the local immune response. 78 As in Crohn's, animal models of ileitis and colitis also exhibit lymphangiogenesis in the lymph nodes and lymphatic-associated TLOs, in addition to defective lymphatic drainage and pumping, as well as sustained mucosal edema and inflammation.…”

Section: Lymphangiogenesis In Intestinal Inflammationmentioning

confidence: 99%

“…73,78 In Crohn's mesenteric tissue biopsies, granulomatous lymphangitis further propagates inflammation as CD20þ B-cell rich TLOs reside along the mesenteric lymphatic vessels inhibiting flow and likely modulating the local immune response. 78 As in Crohn's, animal models of ileitis and colitis also exhibit lymphangiogenesis in the lymph nodes and lymphatic-associated TLOs, in addition to defective lymphatic drainage and pumping, as well as sustained mucosal edema and inflammation. 79,80 Expansion of the mesenteric adipose tissue, termed ''fat-wrapping'' or ''creeping fat,'' is a hallmark of Crohn's.…”

Section: Lymphangiogenesis In Intestinal Inflammationmentioning

confidence: 99%

Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?

Abouelkheir

Upchurch

Rutkowski

2017

Exp Biol Med (Maywood)

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Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes – a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation. Impact statement Inflammatory progression is present in acute and chronic tissue pathologies throughout the body. Lymphatic vessels play physiological roles relevant to all medical fields as important regulators of fluid balance, immune cell trafficking, and immune identity. Lymphangiogenesis is often concurrent with inflammation and can potentially aide or worsen disease progression. How new lymphatic vessels impact inflammation and by which mechanism is an important consideration in current and future clinical therapies targeting inflammation and/or vasculogenesis. This review identifies, across a range of tissue-specific pathologies, the current understanding of inflammation-associated lymphangiogenesis in the progression or resolution of inflammation.

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Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

263

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

Cited by 78 publications

References 21 publications

The Lymphatic System: Integral Roles in Immunity

The Lymphatic System: Integral Roles in Immunity

Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?

Lymphatic Vessel Network Structure and Physiology

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