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Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain
Perivascular macrophages (pvMs) are important for brain drainage and immune regulation. Here the authors analyse various reporter mouse strains for finer mapping of pvM subsets and lineage differentiation, and propose CX3CR1negative and CD45low as additional markers of intermediate pvMs for studying this heterogenous population.
- C. Siret
- , M. van Lessen
- & S. A. van de Pavert
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Article
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Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures
Loss of canonical Notch signaling in vascular endothelial cells induces spontaneous formation of proto-typical tertiary lymphoid structures in mouse kidney, liver and lungs, which form around central arteries that acquire a high endothelial cell signature
- Susanne Fleig
- , Tamar Kapanadze
- & Florian P. Limbourg
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Article
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Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance
Immune cells mostly enter lymph nodes (LN) from blood circulation, but whether afferent lymphatics contributes to LN entry is unclear. Here, the authors show, using a photo-convertible reporter, that T cells in afferent lymphatics frequently enter LN and become arrested in the subcapsular sinus, with chemokines and integrins further guiding their migration in the LN.
- Rieke Martens
- , Marc Permanyer
- & Reinhold Förster
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Article
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Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions
Lymphatic endothelial cells (LECs) can cross-present antigen to naïve CD8+ T cells, but the significance of this interaction was unclear. Here the authors show that LECs directly induce CD8+ T cell differentiation with memory-like phenotypes, migration patterns and transcriptome, which can later be recalled to promote effector immunity and protection from Listeria infection.
- Efthymia Vokali
- , Shann S. Yu
- & Melody A. Swartz
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Article
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Brain-to-cervical lymph node signaling after stroke
Brain damage induces systemic inflammation, but insights and implication of this induction is still unclear. Here the authors show, using rat and mouse focal cerebral ischemia models, that the damaged brain signals via the VEGF-C/VEFGR3 axis to activate inflammatory responses in the draining cervical lymph nodes to induce systemic inflammation.
- Elga Esposito
- , Bum Ju Ahn
- & Kazuhide Hayakawa
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Article
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Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
Lymphangiogenesis occurs in the context of systemic inflammation and development but has not been reported for the lymphatics that surround the CNS. Here the authors show that in the context of experimental autoimmune encephatlitis, lymphangiogenesis occurs at the cribriform plate, but not the meninges, and contributes to immune cell and antigen drainage.
- Martin Hsu
- , Aditya Rayasam
- & Zsuzsanna Fabry
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Article
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Regulation of T cell afferent lymphatic migration by targeting LTβR-mediated non-classical NFκB signaling
Lymphotoxin beta receptor (LTβR) signalling regulates leukocyte migration through the lymphatic endothelial layers. Here, the authors show that treatment of an LTβR-derived decoy peptide can target the non-classical NFκB pathway to inhibit T cell and dendritic cell migration and ameliorate contact hypersensitivity in mouse models.
- Wenji Piao
- , Yanbao Xiong
- & Jonathan S. Bromberg
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Article
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Migratory dendritic cells acquire and present lymphatic endothelial cell-archived antigens during lymph node contraction
Viral infection and vaccination both induce lasting persistence of antigens for protective responses. Here the authors show that migratory dendritic cells, independent of the transcription factor BatF3 for their development, contribute to “archived antigen” exchange with lymphatic endothelial cells.
- Ross M. Kedl
- , Robin S. Lindsay
- & Beth A. Jirón Tamburini
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Article
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Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis
The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor.
- Lalit Kumar Dubey
- , Praneeth Karempudi
- & Nicola L. Harris
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Article
| Open Access
Topical tacrolimus for the treatment of secondary lymphedema
Secondary lymphedema is a debilitating disease with no cure. Here the authors show that topical application of an FDA-approved anti-T cell drug tacrolimus potently prevents development and alleviates pathologic changes of established lymphedema in mice, suggesting a new treatment for human patients.
- Jason C. Gardenier
- , Raghu P. Kataru
- & Babak J. Mehrara
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Article
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Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration
Lymphotoxin regulates lymphoid organ architecture and adhesion molecules involved in lymphocyte trafficking. Here the authors show that lymphotoxin produced by regulatory T cells promotes their migration to the draining lymph nodes by engaging its cognate receptor on lymphatic endothelial cells.
- C. Colin Brinkman
- , Daiki Iwami
- & Jonathan S. Bromberg
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Article
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Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
Pathological lymphangiogenesis is associated with various eye diseases. Here the authors show that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis in the eye by regulating the crosstalk among VEGF-C, podoplanin and integrin pathways, and thus may represent a useful therapeutic target.
- Wei-Sheng Chen
- , Zhiyi Cao
- & Noorjahan Panjwani
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Article
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Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination
Adverse life events have been associated with reduced survival in cancer patients. Here, the authors explore the mechanism responsible and show that chronic stress in mice activates a signalling cascade in macrophages and tumour cells, which results in restructuring of the tumour lymphatic system, promoting metastasis.
- Caroline P. Le
- , Cameron J. Nowell
- & Erica K. Sloan
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Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction
Lymphatic endothelial cells (LECs) induce peripheral tolerance of CD8 T cells. Here the authors show that LECs cannot directly tolerize CD4 T cells as they lack the machinery for loading the antigenic peptide to MHC-II; instead, LECs pass these antigens to dendritic cells that induce CD4 tolerance.
- Sherin J. Rouhani
- , Jacob D. Eccles
- & Victor H. Engelhard
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TH2 cells and their cytokines regulate formation and function of lymphatic vessels
Lymphatic vessels remodel in response to inflammatory conditions and T-cell-secreted cytokines. Here, the authors show that T helper type 2 cells inhibit lymphangiogenesis by secreting IL-4 and IL-13, and that blockade of these cytokines can alleviate allergic asthma symptoms by improving the lymphatic function in mice.
- Kihyuk Shin
- , Raghu P. Kataru
- & Seung-Hyo Lee
Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology