Alexandre Rolland

Publications (6)14.54 Total impact

• Source

  Available from: archives-ouvertes.fr

  Article: The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses.

  Alexandre Rolland, Evelyne Jouvin-Marche, Christophe Viret, Mathias Faure, Hervé Perron, Patrice N Marche
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  ABSTRACT: Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.
  The Journal of Immunology 07/2006; 176(12):7636-44. · 5.79 Impact Factor
• Article: Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans cell histiocytosis.

  Alexandre Rolland, Lydie Guyon, Michelle Gill, Yi-Hong Cai, Jacques Banchereau, Kenneth McClain, A Karolina Palucka
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  ABSTRACT: Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a reactive proliferative disease of unknown pathogenesis. Current therapies are based on nonspecific immunosuppression. Because multiple APCs, including Langerhans cells and macrophages, are involved in the lesion formation, we surmised that LCH is a disease of myeloid blood precursors. We found that lin(-) HLA-DR(+)CD11c-+ precursors of dendritic cells, able to give rise to either Langerhans cells or macrophages, are significantly (p = 0.004) increased in the blood of LCH patients. The analysis of serum cytokines in 24 patients demonstrated significantly elevated levels of hemopoietic cytokines such as fms-like tyrosine kinase ligand (FLT3-L, a dendritic cell-mobilizing factor, approximately 2-fold) and M-CSF ( approximately 4-fold). Higher levels of these cytokines correlated with patients having more extensive disease. Serum levels of FLT3-L and M-CSF were highest in high risk patients with extensive skin and/or multisystem involvement. Finally, patients with bone lesions had relatively higher levels of M-CSF and of stem cell factor. Thus, early hemopoietic cytokines such as FLT3-L, stem cell factor, and M-CSF maybe relevant in LCH pathogenesis and might be considered as novel therapeutic targets.
  The Journal of Immunology 04/2005; 174(5):3067-71. · 5.79 Impact Factor
• Article: Correlation between disease severity and in vitro cytokine production mediated by MSRV (multiple sclerosis associated retroviral element) envelope protein in patients with multiple sclerosis.

  Alexandre Rolland, Evelyne Jouvin-Marche, Marina Saresella, Pasquale Ferrante, Rosella Cavaretta, Alain Créange, Patrice Marche, Hervé Perron
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  ABSTRACT: MSRV is a retroviral element previously isolated in cell cultures from patients with multiple sclerosis. It is part of a new multi-copy endogenous retrovirus family named HERV-W and displays pro-inflammatory properties both in vitro in human PBMC cultures and in vivo in a humanized SCID mice model. In the present study, we have evaluated potential links between the pro-inflammatory properties of MSRV envelope protein and MS disease. Thus, cytokine productions mediated by the surface unit of MSRV envelope protein were evaluated in PBMC of MS patients and compared with healthy controls. Divergent reactivity to ENV-SU between MS and control PBMC was observed and was reflected by a significant increase of IFN-gamma, IL-6 and IL-12p40 production by the tested MS population. Interestingly, the overproduction of IL-6 and IL-12p40 was found to correlate with disease severity (EDSS) in most patients. Altogether our data suggest that MSRV envelope protein may induce an abnormal cytokine secretion, thus contributing to the inflammatory process in MS.
  Journal of Neuroimmunology 04/2005; 160(1-2):195-203. · 2.96 Impact Factor
• Article: Increased Blood Myeloid Dendritic Cells and Dendritic Cell-Poietins in Langerhans Cell Histiocytosis1

  Alexandre Rolland, Lydie Guyon, Michelle Gill, Yi-Hong Cai, Jacques Banchereau, Kenneth McClain, A. Karolina Palucka
  [show abstract] [hide abstract]
  ABSTRACT: Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a reactive proliferative disease of unknown patho- genesis. Current therapies are based on nonspecific immunosuppression. Because multiple APCs, including Langerhans cells and macrophages, are involved in the lesion formation, we surmised that LCH is a disease of myeloid blood precursors. We found that lin HLA-DRCD11c- precursors of dendritic cells, able to give rise to either Langerhans cells or macrophages, are significantly (p 0.004) increased in the blood of LCH patients. The analysis of serum cytokines in 24 patients demonstrated significantly elevated levels of hemopoietic cytokines such as fms-like tyrosine kinase ligand (FLT3-L, a dendritic cell-mobilizing factor, 2-fold) and M-CSF (4-fold). Higher levels of these cytokines correlated with patients having more extensive disease. Serum levels of FLT3-L and M-CSF were highest in high risk patients with extensive skin and/or multisystem involvement. Finally, patients with bone lesions had relatively higher levels of M-CSF and of stem cell factor. Thus, early hemopoietic cytokines such as FLT3-L, stem cell factor, and M-CSF maybe relevant in LCH pathogenesis and might be considered as novel therapeutic targets. The Journal of Immunology, 2005, 174: 3067-3071. (G-CSF, GM-CSF, and fms-like tyrosine kinase ligand (FLT3-L) or activate them (IFN-). Among those, FLT3-L is a growth factor for early hemopoietic progenitor cells (17). FLT3-L has been shown to expand distinct subsets of DCs) in mice in vivo (18, 19). Administration of FLT3-L to healthy human volunteers (HVs) and cancer patients leads to mobilization of both human DC subsets present in the blood, i.e., plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) (15, 20). FLT3-L can be detected in the serum of healthy HVs (21), and it can be elevated in diseases with under- lying DC pathology. For example, systemic lupus erythematosus, an autoimmune disease where interplay between distinct DC sub- sets may play a role (12), is associated with high serum levels of FLT3-L (21). Therefore, we surmised that dysregulation of DC- poietins might also explain LCH-associated pathology.
• Article: Immune and Clinical Responses in Patients with Metastatic Melanoma to CD34 Progenitor-derived Dendritic Cell Vaccine1

  Jacques Banchereau, A. Karolina Palucka, Madhav Dhodapkar, Susan Burkeholder, Nicolas Taquet, Alexandre Rolland, Sybil Taquet, Sebastien Coquery, Knut M. Wittkowski, Nina Bhardwaj, Luis Pineiro, Ralph Steinman
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  ABSTRACT: Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201 patients with metastatic melanoma received injections s.c. of CD34 progenitor-derived autologous dendritic cells (DCs), which in- cluded Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens ((MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100), as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P 0.015).
• Article: The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses.

  Alexandre Rolland, Evelyne Jouvin-Marche, Christophe Viret, Mathias Faure, Hervé Perron, Patrice Marche
  [show abstract] [hide abstract]
  ABSTRACT: Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.