Monocyte-derived Wnt5a regulates inflammatory lymphangiogenesis

Sessa, Roberto; Yuen, Don; Wan, Stephanie; Rosner, Michael C.; Padmanaban, Preethi; Ge, Shaokui; Smith, April N.; Fletcher, Russell B.; Baudhuin-Kessel, Ariane; Yamaguchi, Terry P.; Lang, Richard A.; Chen, Lu

doi:10.1038/cr.2015.105

Cited by 19 publications

(17 citation statements)

References 13 publications

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“…3,6,8 For vascular analysis, whole-mount corneas were harvested at the end of the 8-week study, and fixed in acetone for immunostaining with primary antibodies against LYVE-1 (rabbit-anti-mouse; Abcam, Inc., Cambridge, MA, USA) and CD31 (rat-anti-mouse; Santa Cruz Biotechnology, Santa Cruz, CA, USA), which were visualized by FITC conjugated donkey-anti-rabbit and Cy3 conjugated donkey-anti-rat secondary antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA, USA), respectively. For macrophage analysis, whole-mount corneas were harvested at 2 weeks post transplantation and stained with rat-anti-mouse F4/80 antibody (Abcam, Inc.), which was recognized by a FITC conjugated donkey-anti-rat secondary antibody (Jackson ImmunoResearch Laboratories).…”

Section: Methodsmentioning

confidence: 99%

“…Quantification analysis was performed as reported previously. 3,6,8 Vascular structures stained as CD31 + LYVE-1 + were defined as lymphatic vessels and stained as CD31 + LYVE-1 − were defined as blood vessels. Vessel coverage area was quantified using ImageJ software (http://imagej.nih.gov/ij/; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA) and normalized to total corneal area to obtain a percentage coverage score for each sample.…”

Section: Methodsmentioning

confidence: 99%

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Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Zhang

Sessa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeCorneal transplantation remains the last hope for vision restoration, and lymphangiogenesis (LG) is a primary mediator of transplant rejection. This study was to investigate the specific role of angiopoietin-2 (Ang-2) in transplantation-associated LG and graft rejection.MethodsOrthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice to assess the effects of Ang-2 blockade via neutralizing antibody. Grafts were evaluated in vivo by ophthalmic slit-lamp biomicroscopy and anterior segment optical coherence tomography (OCT) up to 8 weeks after surgery. Additionally, whole-mount corneas were analyzed for lymphatic and blood vessels and macrophages by immunofluorescent microscopy, and draining lymph nodes were assessed for donor-derived cells by flow cytometry.ResultsAnti-Ang-2 treatment significantly suppressed LG and graft rejection. In this study, we achieved 75% suppression of LG and 80% graft survival. Our approach also inhibited donor-derived cell trafficking to draining lymph nodes and affected macrophage morphologic phenotypes in the grafted corneas. Additionally, Ang-2 blockade also reduced central corneal thickening, a parameter strongly associated with graft rejection.ConclusionsAng-2 is critically involved in corneal transplant rejection and anti-Ang-2 treatment significantly improves the outcomes of corneal grafts. Moreover, we have shown that anterior segment OCT offers a new tool to monitor murine corneal grafts in vivo. This study not only reveals new mechanisms for transplant rejection, but also offers a novel strategy to treat it.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Zhang

Sessa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

Self Cite

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“…Several lines of evidence indicate that Wnt5A signaling is important for macrophage differentiation and survival. When stimulated with granulocyte monocyte-colony stimulator factor (GM-CSF), bone marrow from Wnt5A conditional knock-out mice show less potency to differentiate into F4/80 + and CD11b + macrophages compared to bone marrow from control mice [48]. Furthermore, Please use Adobe Acrobat Reader to read this book chapter for free.…”

Section: Role Of Wnt5a Signaling In Immune Responsementioning

confidence: 99%

Wnt5A Signaling AntagonizesLeishmania donovaniInfection

Chakraborty¹,

Maity²,

Sen³

2020

Vector-Borne Diseases - Recent Developments in Epidemiology and Control

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Infection by the parasite Leishmania donovani causes Visceral Leishmaniasis, a deadly disease if not properly treated. L. donovani captures the immune defense potential of host macrophages. It disrupts immune homeostasis at least partly by inducing expression of anti-inflammatory cytokines and altering the cellular cytoskeletal framework, thereby creating a niche for its own survival. While inhibition of macrophage Wnt5A signaling promotes infection by the parasite, activation of Wnt5A signaling significantly dampens infection. Experimental evidence suggests that the antagonistic effect of Wnt5A signaling on parasite infection in macrophages may be on account of its influence on the actin cytoskeleton. Importantly, the inhibitory effect of Wnt5A on infection is sustained independent of drug sensitivity and resistance. Keeping in mind that drugs used to treat Visceral Leishmaniasis are quite toxic and the parasite develops drug resistance, revamping host Wnt5A signaling may be useful for eliminating infection independent of drug sensitivity or resistance.

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“…Indeed, a number of studies found that Wnt3a/β-cat signaling induced anti-inflammatory cytokine signatures, such as reduced TNFα levels (30), reduced IL6 levels (63, 64), and elevated IL4 targets [Arg1, CD206/MR, Fizz1, YM1 (27); Figure 3]. However, Wnt5a could also generate anti-inflammatory macrophage phenotypes in certain contexts (34, 38). In addition, Wnt3a/β-cat signaling could be pro-inflammatory in microglia (28) and β-cat could pair with a dsRNA nucleic acid sensor protein to induce IFN-β production downstream of Listeria infection (65).…”

Section: Wnt Signaling In Macrophage Differentiation and Maintenancementioning

confidence: 99%

Macrophages as a Source and Recipient of Wnt Signals

et al. 2019

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Macrophages are often viewed through the lens of their core functions, but recent transcriptomic studies reveal them to be largely distinct across tissue types. While these differences appear to be shaped by their local environment, the key signals that drive these transcriptional differences remain unclear. Since Wnt signaling plays established roles in cell fate decisions, and tissue patterning during development and tissue repair after injury, we consider evidence that Wnt signals both target and are affected by macrophage functions. We propose that the Wnt gradients present in developing and adult tissues effectively shape macrophage fates and phenotypes. We also highlight evidence that macrophages, through an ability to dispatch Wnt signals, may couple tissue debridement and matrix remodeling with stem cell activation and tissue repair.

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Monocyte-derived Wnt5a regulates inflammatory lymphangiogenesis

Cited by 19 publications

References 13 publications

Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants

Wnt5A Signaling AntagonizesLeishmania donovaniInfection

Macrophages as a Source and Recipient of Wnt Signals

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