B Cell-Driven Lymphangiogenesis in Inflamed Lymph Nodes Enhances Dendritic Cell Mobilization

Angeli, Véronique; Ginhoux, Florent; Llodrá, Jaime; Quéméneur, Laurence; Frenette, Paul S.; Skobe, Mihaela; Jessberger, Rolf; Mérad, Miriam; Randolph, Gwendalyn J.

doi:10.1016/j.immuni.2006.01.003

Cited by 396 publications

(233 citation statements)

References 44 publications

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“…Although not assessed in this study, it would be of interest to investigate the potential role of lymph node lymphangiogenesis in the control of inflammation (Angeli et al, 2006;Halin et al, 2007). The increased draining capacity and resolution of chronic skin inflammation might be, at least in part, mediated by enhanced lymph node lymphangiogenesis in addition to the increased lymphangiogenesis that we observed in the lesional skin itself.…”

Section: Discussionmentioning

confidence: 88%

Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation

Huggenberger¹,

Ullmann²,

Proulx³

et al. 2010

J Cell Biol

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The role of lymphangiogenesis in inflammation has remained unclear. To investigate the role of lymphatic versus blood vasculature in chronic skin inflammation, we inhibited vascular endothelial growth factor (VEGF) receptor (VEGFR) signaling by function-blocking antibodies in the established keratin 14 (K14)-VEGF-A transgenic (Tg) mouse model of chronic cutaneous inflammation. Although treatment with an anti-VEGFR-2 antibody inhibited skin inflammation, epidermal hyperplasia, inflammatory infiltration, and angiogenesis, systemic inhibition of VEGFR-3, surprisingly, increased inflammatory edema formation and inflammatory cell accumulation despite inhibition of lymphangiogenesis. Importantly, chronic Tg delivery of the lymphangiogenic factor VEGF-C to the skin of K14-VEGF-A mice completely inhibited development of chronic skin inflammation, epidermal hyperplasia and abnormal differentiation, and accumulation of CD8 T cells. Similar results were found after Tg delivery of mouse VEGF-D that only activates VEGFR-3 but not VEGFR-2. Moreover, intracutaneous injection of recombinant VEGF-C156S, which only activates VEGFR-3, significantly reduced inflammation. Although lymphatic drainage was inhibited in chronic skin inflammation, it was enhanced by Tg VEGF-C delivery. Together, these results reveal an unanticipated active role of lymphatic vessels in controlling chronic inflammation. Stimulation of functional lymphangiogenesis via VEGFR-3, in addition to antiangiogenic therapy, might therefore serve as a novel strategy to treat chronic inflammatory disorders of the skin and possibly also other organs.

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Section: Discussionmentioning

confidence: 88%

Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation

Huggenberger¹,

Ullmann²,

Proulx³

et al. 2010

J Cell Biol

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“…In this issue of Immunity, Angeli et al (2006) provide the first evidence that remodeling of the lymphatic network within LNs and in peripheral tissues enhances DC migration after immunization and that this process depends on the presence of B cells within the LN.…”

Section: An Unexpected Connection: Lymph Node Lymphangiogenesis and Dmentioning

confidence: 97%

An Unexpected Connection: Lymph Node Lymphangiogenesis and Dendritic Cell Migration

Halin

Detmar

2006

Immunity

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Migration of antigen-presenting dendritic cells (DCs) through lymphatics to draining lymph nodes (LNs) represents a key step in the initiation of an adaptive immune response. In this issue of Immunity, provide the first evidence that remodeling of the lymphatic network within LNs and in peripheral tissues enhances DC migration after immunization and that this process depends on the presence of B cells within the LN.

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“…Especially blood and intranodal lymphatic vessels form fairly ''linear streets'' from the T cell-B cell zone to the medulla. During an immune response both vessel types are increased in frequency within the outer T cell zone (Angeli et al, 2006). Could it be that PBs only initially adopt a random orientation for their migration in order to search for vessels guiding them to the medulla?…”

mentioning

confidence: 99%