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Dive into the research topics where Cédric Auffray is active.

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Featured researches published by Cédric Auffray.


Annual Review of Immunology | 2009

Blood monocytes: development, heterogeneity, and relationship with dendritic cells.

Cédric Auffray; Michael H. Sieweke; Frederic Geissmann

Monocytes are circulating blood leukocytes that play important roles in the inflammatory response, which is essential for the innate response to pathogens. But inflammation and monocytes are also involved in the pathogenesis of inflammatory diseases, including atherosclerosis. In adult mice, monocytes originate in the bone marrow in a Csf-1R (MCSF-R, CD115)-dependent manner from a hematopoietic precursor common for monocytes and several subsets of macrophages and dendritic cells (DCs). Monocyte heterogeneity has long been recognized, but in recent years investigators have identified three functional subsets of human monocytes and two subsets of mouse monocytes that exert specific roles in homeostasis and inflammation in vivo, reminiscent of those of the previously described classically and alternatively activated macrophages. Functional characterization of monocytes is in progress in humans and rodents and will provide a better understanding of the pathophysiology of inflammation.


Cell | 2013

Nr4a1-Dependent Ly6C(low) Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal

Leo M. Carlin; Efstathios G. Stamatiades; Cédric Auffray; Richard N. Hanna; Leanne Glover; Gema Vizcay-Barrena; Catherine C. Hedrick; H. Terence Cook; Sandra S. Diebold; Frederic Geissmann

Summary The functions of Nr4a1-dependent Ly6Clow monocytes remain enigmatic. We show that they are enriched within capillaries and scavenge microparticles from their lumenal side in a steady state. In the kidney cortex, perturbation of homeostasis by a TLR7-dependent nucleic acid “danger” signal, which may signify viral infection or local cell death, triggers Gαi-dependent intravascular retention of Ly6Clow monocytes by the endothelium. Then, monocytes recruit neutrophils in a TLR7-dependent manner to mediate focal necrosis of endothelial cells, whereas the monocytes remove cellular debris. Prevention of Ly6Clow monocyte development, crawling, or retention in Nr4a1−/−, Itgal−/−, and Tlr7host−/−BM+/+ and Cx3cr1−/− mice, respectively, abolished neutrophil recruitment and endothelial killing. Prevention of neutrophil recruitment in Tlr7host+/+BM−/− mice or by neutrophil depletion also abolished endothelial cell necrosis. Therefore, Ly6Clow monocytes are intravascular housekeepers that orchestrate the necrosis by neutrophils of endothelial cells that signal a local threat sensed via TLR7 followed by the in situ phagocytosis of cellular debris.


Journal of Experimental Medicine | 2009

CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation.

Cédric Auffray; Darin K. Fogg; Emilie Narni-Mancinelli; Brigitte Senechal; Céline Trouillet; Noah Saederup; Julia Leemput; Karine Bigot; Laura Campisi; Marc Abitbol; Thierry Molina; Israel F. Charo; David A. Hume; Ana Cumano; Grégoire Lauvau; Frederic Geissmann

CX3CR1 expression is associated with the commitment of CSF-1R+ myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R+ CX3CR1+ macrophage/DC precursor (MDP) with other DC precursors and the role of CX3CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to conventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1+ inflammatory monocytes that differentiate into TipDCs during infection. CX3CR1 deficiency selectively impairs the recruitment of blood Gr1+ monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs.


Journal of Immunology | 2005

Peripheral CD8+CD25+ T Lymphocytes from MHC Class II-Deficient Mice Exhibit Regulatory Activity

Boris Bienvenu; Bruno Martin; Cédric Auffray; Corinne Cordier; Chantal Bécourt; Bruno Lucas

We characterized CD8+ T cells constitutively expressing CD25 in mice lacking the expression of MHC class II molecules. We showed that these cells are present not only in the periphery but also in the thymus. Like CD4+CD25+ T cells, CD8+CD25+ T cells appear late in the periphery during ontogeny. Peripheral CD8+CD25+ T cells from MHC class II-deficient mice also share phenotypic and functional features with regulatory CD4+CD25+ T cells: in particular, they strongly express glucocorticoid-induced TNFR family-related gene, CTLA-4 and Foxp3, produce IL-10, and inhibit CD25− T cell responses to anti-CD3 stimulation through cell contacts with similar efficiency to CD4+CD25+ T cells. However, unlike CD4+CD25+ T cells CD8+CD25+ T cells from MHC class II-deficient mice strongly proliferate and produce IFN-γ in vitro in response to stimulation in the absence of exogenous IL-2.


Blood | 2009

Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development

Armelle Le Campion; Marie-Claude Gagnerault; Cédric Auffray; Chantal Bécourt; Maud Poitrasson-Rivière; Eliette Lallemand; Boris Bienvenu; Bruno Martin; Françoise Lepault; Bruno Lucas

Lymphopenia is thought to be a major cause of tolerance breakdown. In a lymphopenic environment, self-recognition events induce some T cells to expand strongly (a mechanism known as spontaneous proliferation). In this study, we show that in C57BL/6 mice, the repertoire resulting from lymphopenia-induced spontaneous CD4(+) T-cell proliferation included a proportion of regulatory T cells as large as that observed in a normal mouse, and no autoimmune disorder was observed. By contrast, in nonobese diabetic mice, differences in the ability of conventional and regulatory T cells to expand in response to lymphopenia led to an unbalance between these 2 T-cell compartments at the expense of regulatory T cells, resulting in the onset of autoimmune diseases. Notably, this accounted for the rapid transfer of diabetes with small numbers of BDC2.5 CD4(+) T cells. Thus, lymphopenia does not itself induce autoimmunity, but it should be considered as a cofactor for the development of autoimmune disorders.


Journal of Cell Science | 2012

Semaphorin 3A elevates endothelial cell permeability through PP2A inactivation.

Armelle Le Guelte; Eva-Maria Galan-Moya; Julie Dwyer; Lucas Treps; Garance Kettler; Jagoda K. Hebda; Sonia M. Dubois; Cédric Auffray; Hervé Chneiweiss; Nicolas Bidère; Julie Gavard

Summary VE-cadherin-mediated cell–cell junction weakening increases paracellular permeability in response to both angiogenic and inflammatory stimuli. Although Semaphorin 3A has emerged as one of the few known anti-angiogenic factors to exhibit pro-permeability activity, little is known about how it triggers vascular leakage. Here we report that Semaphorin 3A induced VE-cadherin serine phosphorylation and internalisation, cell–cell junction destabilisation, and loss of barrier integrity in brain endothelial cells. In addition, high-grade glioma-isolated tumour-initiating cells were found to secrete Semaphorin 3A, which promoted brain endothelial monolayer permeability. From a mechanistic standpoint, Semaphorin 3A impinged upon the basal activity of the serine phosphatase PP2A and disrupted PP2A interaction with VE-cadherin, leading to cell–cell junction disorganization and increased permeability. Accordingly, both pharmacological inhibition and siRNA-based knockdown of PP2A mimicked Semaphorin 3A effects on VE-cadherin. Hence, local Semaphorin 3A production impacts on the PP2A/VE-cadherin equilibrium and contributes to elevated vascular permeability.


Proceedings of the National Academy of Sciences of the United States of America | 2013

Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4+ T cells

Arnaud Pommier; Alexandra Audemard; Aurélie Durand; Renée Lengagne; Arnaud Delpoux; Bruno Martin; Laetitia Douguet; Armelle Le Campion; Masashi Kato; Marie-Françoise Avril; Cédric Auffray; Bruno Lucas; Armelle Prévost-Blondel

The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression. Here, we find that regulatory CD4+ T cells accumulate in the skin, the spleen, and tumor-draining lymph nodes of MT/ret mice not developing vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. Moreover, they inhibit tumor cell proliferation in vitro through a reactive oxygen species-dependent mechanism, and both their depletion and reactive oxygen species neutralization in vivo increased tumor cell dissemination. Altogether, our data suggest that regulatory CD4+ T cells favor tumor progression, in part, by inhibiting recruitment and/or differentiation of inflammatory monocytes in the skin.


Nature Communications | 2013

Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells

Bruno Martin; Cédric Auffray; Arnaud Delpoux; Arnaud Pommier; Aurélie Durand; Céline Charvet; Philippe Yakonowsky; Nelly Bonilla; Alexandra Audemard; Tim Sparwasser; Benoît L. Salomon; Bernard Malissen; Bruno Lucas

Upon activation, naive CD4 T cells differentiate into a variety of T-helper-cell subsets characterized by different cytokine production and functions. Currently, lineage commitment is considered to depend mostly on the environmental context to which naive CD4 T cells are exposed. Here we challenge this model based on the supposed homogeneity of the naive CD4 T-cell compartment. We show that peripheral naive CD4 T cells can be subdivided into two subsets according to Ly-6C expression. Furthermore, the two newly defined subsets (Ly-6C(-) and Ly-6C(+) naive CD4 T cells) are not equal in their intrinsic ability to commit into the induced regulatory T-cell lineage. Finally, phenotypic analysis, imaging and adoptive transfer experiments reveal that Ly-6C expression is modulated by self-recognition, allowing the dichotomization of the naive CD4 T-cell compartment into two cell subsets with distinct self-reactivity. Altogether, our results show that naive CD4 T cells with the highest avidity for self are prone to differentiate into regulatory T cells.


Journal of Immunology | 2012

IL-2 and IL-7 Determine the Homeostatic Balance between the Regulatory and Conventional CD4+ T Cell Compartments during Peripheral T Cell Reconstitution

Armelle Le Campion; Arnaud Pommier; Arnaud Delpoux; Laurence Stouvenel; Cédric Auffray; Bruno Martin; Bruno Lucas

Work over the last decades has led to the identification of the factors that influence the survival and homeostasis of conventional T cells. IL-7 and TCR signaling promote the survival of naive CD4+ and CD8+ T cells in lymphoreplete mice and their proliferation in a lymphopenic environment, whereas survival and homeostatic proliferation of memory CD4+ and CD8+ T cells crucially depend on a combination of IL-7 and IL-15. In contrast, there is little information regarding the factors driving the proliferation of regulatory CD4+ T cells in response to lymphopenia. In this study, we investigated whether regulatory CD4+ T cell proliferation in response to lymphopenia was guided by classical homeostatic resources, such as IL-2, IL-7, or TCR–MHC interactions. Altogether, our data suggest that, although homeostatic proliferation of conventional naive CD4+ T cells is closely related to IL-7 levels, the proliferation of regulatory CD4+ T cells in response to lymphopenia appears to be primarily controlled by IL-2. The capacity of IL-7 to augment conventional T cell proliferation with minimal concomitant regulatory T cell expansion may be clinically exploitable in the treatment of patients with lymphopenia, especially in the case of chronic viral diseases or cancer immunotherapy.


Journal of Immunology | 2015

Foxo1 Is a T Cell–Intrinsic Inhibitor of the RORγt-Th17 Program

Alexandra Lainé; Bruno Martin; Marine Luka; Cédric Auffray; Bruno Lucas; Georges Bismuth; Céline Charvet

An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator of the Th17 program. Using mixed bone marrow chimeras and Foxo1-deficient mice, we demonstrate that this control is effective in vivo, as well as in vitro during differentiation assays of naive T cells with specific inhibitor of Foxo1 or inhibitors of the PI3K/Akt pathway acting upstream of Foxo1. Consistently, expressing this transcription factor in T cells strongly decreases Th17 generation in vitro as well as transcription of both IL-17A and IL-23R RORγt-target genes. Finally, at the molecular level, we demonstrate that Foxo1 forms a complex with RORγt via its DNA binding domain to inhibit RORγt activity. We conclude that Foxo1 is a direct antagonist of the RORγt-Th17 program acting in a T cell–intrinsic manner.

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Aurélie Durand

Paris Descartes University

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Nelly Bonilla

Paris Descartes University

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Arnaud Delpoux

University of California

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Frederic Geissmann

Memorial Sloan Kettering Cancer Center

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Bruno Martin

French Institute of Health and Medical Research

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Arnaud Pommier

Cold Spring Harbor Laboratory

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Matthieu Rivière

Paris Descartes University

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