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Dive into the research topics where Wendy Peters is active.

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Featured researches published by Wendy Peters.


Nature Immunology | 2002

Langerhans cells renew in the skin throughout life under steady-state conditions

Miriam Merad; Markus G. Manz; Holger Karsunky; Amy J. Wagers; Wendy Peters; Israel F. Charo; Irving L. Weissman; Jason G. Cyster; Edgar G. Engleman

Langerhans cells (LCs) are bone marrow (BM)–derived epidermal dendritic cells (DCs) that represent a critical immunologic barrier to the external environment, but little is known about their life cycle. Here, we show that in lethally irradiated mice that had received BM transplants, LCs of host origin remained for at least 18 months, whereas DCs in other organs were almost completely replaced by donor cells within 2 months. In parabiotic mice with separate organs, but a shared blood circulation, there was no mixing of LCs. However, in skin exposed to ultraviolet light, LCs rapidly disappeared and were replaced by circulating LC precursors within 2 weeks. The recruitment of new LCs was dependent on their expression of the CCR2 chemokine receptor and on the secretion of CCR2-binding chemokines by inflamed skin. These data indicate that under steady-state conditions, LCs are maintained locally, but inflammatory changes in the skin result in their replacement by blood-borne LC progenitors.


Journal of Clinical Investigation | 2007

Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites

Chia-Lin Tsou; Wendy Peters; Yue Si; Sarah Slaymaker; Ara M. Aslanian; Stuart P. Weisberg; Matthias Mack; Israel F. Charo

Monocyte recruitment to sites of inflammation is regulated by members of the chemokine family of chemotactic cytokines. However, the mechanisms that govern the migration of monocytes from bone marrow to blood and from blood to inflamed tissues are not well understood. Here we report that CC chemokine receptor 2 (CCR2) is highly expressed on a subpopulation of blood monocytes whose numbers are markedly decreased in CCR2(-/-) mice. In bone marrow, however, CCR2(-/-) mice had an increased number of monocytes, suggesting that CCR2 is critical for monocyte egress. Intravenous infusion of ex vivo-labeled WT or CCR2(-/-) bone marrow into WT recipient mice demonstrated that CCR2 is necessary for efficient monocyte recruitment from the blood to inflamed tissue. Analysis of mice lacking monocyte chemoattractant protein-1 (MCP-1), MCP-3, MCP-5, or MCP-2 plus MCP-5 revealed that MCP-3 and MCP-1 are the CCR2 agonists most critical for the maintenance of normal blood monocyte counts. These findings provide evidence that CCR2 and MCP-3/MCP-1 are critical for monocyte mobilization and suggest new roles for monocyte chemoattractants in leukocyte homeostasis.


Proceedings of the National Academy of Sciences of the United States of America | 2001

Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis

Wendy Peters; Holly M. Scott; Henry F. Chambers; JoAnne L. Flynn; Israel F. Charo; Joel D. Ernst

Although the protective cellular immune response to Mycobacterium tuberculosis requires recruitment of macrophages and T lymphocytes to the site of infection, the signals that regulate this trafficking have not been defined. We investigated the role of C-C chemokine receptor 2 (CCR2)-dependent cell recruitment in the protective response to M. tuberculosis. CCR2−/− mice died early after infection and had 100-fold more bacteria in their lungs than did CCR2+/+ mice. CCR2−/− mice exhibited an early defect in macrophage recruitment to the lung and a later defect in recruitment of dendritic cells and T cells to the lung. CCR2−/− mice also had fewer macrophages and dendritic cells recruited to the mediastinal lymph node (MLN) after infection. T cell migration through the MLN was similar in CCR2−/− and CCR2+/+ mice. However, T cell priming was delayed in the MLNs of the CCR2−/− mice, and fewer CD4+ and CD8+ T cells primed to produce IFN-γ accumulated in the lungs of the CCR2−/− mice. These data demonstrate that cellular responses mediated by activation of CCR2 are essential in the initial immune response and control of infection with M. tuberculosis.


Journal of Experimental Medicine | 2004

Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes

Chunfeng Qu; Emmerson W. Edwards; Frank Tacke; Veronique Angeli; Jaime Llodra; Guzman Sanchez-Schmitz; Alexandre Garin; Nasreen S. Haque; Wendy Peters; Nico van Rooijen; Carmen Sánchez-Torres; Jonathan S. Bromberg; Israel F. Charo; Steffen Jung; Sergio A. Lira; Gwendalyn J. Randolph

Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX3CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX3CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1int monocyte population, and the number of latex+ DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1int monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1int monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.


Journal of Clinical Investigation | 2001

Targeted deletion of CX3CR1 reveals a role for fractalkine in cardiac allograft rejection

Christopher A. Haskell; Wayne W. Hancock; David J. Salant; Wei Gao; Vilmos Csizmadia; Wendy Peters; Kerrie L. Faia; Omar Fituri; James B. Rottman; Israel F. Charo

Fractalkine (Fk) is a structurally unusual member of the chemokine family. To determine its role in vivo, we generated mice with a targeted disruption of CX3CR1, the receptor for Fk. CX3CR1–/– mice were phenotypically indistinguishable from wild-type mice in a pathogen-free environment. In response to antibody-induced glomerulonephritis, CX3CR1–/– and CX3CR1+/+ mice had similar levels of proteinuria and injury. CX3CR1–/– and CX3CR1+/+ mice also developed similar levels of disease in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. We performed heterotopic MHC class I/II cardiac transplants from BALB/c mice into C57BL/6 mice. In the absence of cyclosporin A (CsA), there was no difference in graft survival time between CX3CR1–/– and CX3CR1+/+ recipient mice. However, in the presence of subtherapeutic levels of CsA, graft survival time was significantly increased in the CX3CR1–/– mice. Characterization of cells infiltrating the grafts revealed a selective reduction in natural killer cells in the CX3CR1–/– recipients in the absence of CsA and a reduction in macrophages, natural killer cells, and other leukocytes in the presence of CsA. We conclude that Fk plays an important role in graft rejection. The development of CX3CR1 antagonists may allow reductions in the doses of immunosuppressive drugs used in transplantation.


Current Opinion in Lipidology | 2001

Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice.

Wendy Peters; Israel F. Charo

Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, but the signals that initiate their recruitment to the vessel wall are poorly understood. Here, we review in vivo studies in genetically altered mice that support the notion that monocyte chemoattractant protein-1 (a member of the chemokine family of chemotactic cytokines) and chemokine receptor 2 (its cognate receptor) play important roles in this recruitment. An unexpected finding in chemokine receptor 2-knockout mice was the diminished production of interferon-γ, which is a potent macrophage activator. The basis of this cytokine defect is not yet clear, but suggests that chemokines may influence atherosclerotic lesion development at several levels. Understanding the roles of chemokines and cytokines in atherogenesis may provide a basis for the development of future therapeutic agents that are aimed at interrupting monocyte recruitment and activation.


European Journal of Immunology | 2001

Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis

Marc Dupuis; Kimberly Denis-Mize; Allyson LaBarbara; Wendy Peters; Israel F. Charo; Donald M. McDonald; Gary Ott

The mechanisms associated with the immunostimulatory activity of vaccine adjuvants are still poorly understood. We have undertaken a study to determine whether antigen‐presenting cell trafficking is modified by administration of the submicron emulsion adjuvant MF59. We investigated the fate of inflammatory macrophages after intramuscular injection of the antigen herpes simplex virus gD2 with fluorescence‐labeled MF59. A homogenous population of macrophages infiltrated the muscle, internalized adjuvant and expressed markers characteristic of mature macrophages over a 48‐h period. Macrophage influx to the injection site was reduced by 70% in mice deficient for the chemokine receptor 2 (CCR2). Two distinct cell populations were shown to contain fluorescence‐labeled MF59 in the draining lymph node at 48 h post injection. The first population had a round morphology, exhibited bright fluorescence, was located in the subcapsular sinus, and was apoptotic. The second population had a dendritic morphology, was weakly fluorescent, and was located in the T cell area where adjuvant‐containing apoptotic bodies identified by TUNEL labeling were present. We propose that lymph node‐resident dendritic cells can acquire antigen and MF59 after intramuscular immunization by uptake of the apoptotic macrophages.


Journal of Immunology | 2004

CCR2-Dependent Trafficking of F4/80dim Macrophages and CD11cdim/intermediate Dendritic Cells Is Crucial for T Cell Recruitment to Lungs Infected with Mycobacterium tuberculosis

Wendy Peters; Jason G. Cyster; Matthias Mack; Detlef Schlöndorff; Andrea J. Wolf; Joel D. Ernst; Israel F. Charo

We previously reported that CCR2−/− mice are susceptible to Mycobacterium tuberculosis infection. Susceptibility was associated with an early and sustained macrophage trafficking defect, followed by delayed recruitment of dendritic cells (DCs) and T cells to the lungs. However, the relative importance of the lack of CCR2 expression by macrophages and DCs vs T cells in susceptibility to infection was unclear. In this study, we used mixed bone marrow transplantation to create mice in which the genotype of the T cells was either CCR2+/+ or CCR2−/− while maintaining the genotype of the myeloid cells as CCR2+/+. After infection with M. tuberculosis, we found that the genotype of the macrophages and/or DCs, but not that of the T cells, was critical for both T cell and myeloid cell migration to the lungs. Further investigation revealed a critical role for CCR2 in the recruitment of F4/80dim macrophages and CD11cdim/intermediate DCs to the infected lung.


Journal of Immunology | 2000

A Mechanism for the Impaired IFN-γ Production in C-C Chemokine Receptor 2 (CCR2) Knockout Mice: Role of CCR2 in Linking the Innate and Adaptive Immune Responses

Wendy Peters; Marc Dupuis; Israel F. Charo

We have recently shown that mice with a targeted disruption of CCR2, the receptor for monocyte chemoattractant protein-1, have markedly impaired recruitment of macrophages to sites of inflammation. An unexpected finding in the CCR2−/− mice was a dramatic decrease in the production of IFN-γ after challenge with purified protein derivative of Mycobacterium bovis. In this study, we have investigated the mechanism of this cytokine production defect. In vitro, direct activation of splenocytes with CD3/CD28 Abs failed to reveal any differences in IFN-γ production between CCR2+/+ and CCR2−/− mice. However, after immunization, the number of Ag-specific, IFN-γ-producing cells in the draining lymph nodes was decreased by 70% in the CCR2−/− mice, suggesting an in vivo trafficking defect. Direct measurement of cell trafficking with fluorescently labeled CFA revealed a marked decrease in the number of monocytes/macrophages migrating to the site of immunization and to the draining lymph nodes in the CCR2−/− mice. The data suggest that impaired trafficking of APCs in the CCR2−/− mice contributes to the defect in IFN-γ production. These data support the idea that CCR2-positive monocytes/macrophages are critical in linking the innate and adaptive immune responses.


Microcirculation | 2003

Chemokine Receptor 2 (CCR2) in Atherosclerosis, Infectious Diseases, and Regulation of T-Cell Polarization

Israel F. Charo; Wendy Peters

Infiltration of tissues by monocyte‐derived macrophages is a prominent component of a wide‐range of diseases, including atherosclerosis, glomerulonephritis, encephalitis, infectious diseases, and virtually all syndromes characterized by chronic inflammation. The molecular signals responsible for this directed migration are incompletely understood, but members of the chemokine family, especially the monocyte chemoattractant proteins (MCPs) (MCP‐1 to MCP‐5) are emerging as key players. Cells that respond to the MCPs do so because they express chemokine receptor 2 (CCR2), the cognate receptor. This review will summarize evidence supporting a key role for CCR2 in the pathogenesis of atherosclerosis, infections with intracellular pathogens, and regulation of the type I adaptive immune response.

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Marc Dupuis

University of California

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Matthias Mack

University of Regensburg

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Alexandre Garin

Icahn School of Medicine at Mount Sinai

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