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Ciri team 14.pdf

“Immunology of skin allergy
and vaccination”
Leader: JF. NICOLAS
Name: NICOLAS
First Name: Jean-François
CSS n°: 5

Unit: CIRI
Team “Immunology of skin allergy and vaccination”
Our laboratory studies the role of cytotoxic T lymphocytes (CTLs) as pivotal cells for the development of skin allergic diseases and as target cells in the development of new vaccines administered through the skin. 1. Pathophysiology of skin allergic diseases: CD8+ cytotoxic T cells are effectors and CD4+ T cells are
regulatory.
Eczemas (both contact and atopic dermatitis) and drug allergy are the consequence of the breakdown of immune
tolerance to allergens. Our team dissects the mechanisms by which allergens circumvent tolerance and promote
allergic responses, in both mouse models and in humans. We have shown that CD8+ CTLs are mandatory for the
initiation of skin allergic lesions, while CD4+ T cells are endowed with down-regulatory/tolerogenic properties.
In addition, we have developed in vivo or in vitro methods for the diagnosis of penicillin allergy and for
prediction of the sensitizing properties of chemicals. Our ultimate objective consists in developing new strategies
to restore skin tolerance to allergens.
2. New methods of skin vaccination
Skin is an outstanding route to stimulate robust immunity, especially to induce potent CD8+ CTL responses. In
order to optimize vaccine protection in the elderly or in immunosuppressed patients, our team focuses on the
development of intradermal (ID) vaccines (Lyon Biopole projects). Our main goal is to gain insight into the early
cellular and molecular events initiated by antigenic ID microinjection that condition the quality of the cellular
and humoral vaccine protection.
3. Management of the projects.
All our projects are performed at the interface of fundamental/translational/clinical research in preclinical
models in mice (INSERM U851) and/or in eczema and drug allergy patients (CH Lyon-sud). They also receive
the support of the Phase I-clinical research unit URSI-LS and of the biobank Allergobiothèque (Lyon Hospitals).
Of note, our team manages the drug allergy reference center for the Rhône-Alpes/Auvergne area.
Selected publications (5)
1. Vanbervliet B, Akdis M, Vocanson M, Rozières A, Benetière J, Rouzaire P, Akdis C, Nicolas JF, Hennino A. Histamine receptor H1 signaling on dendritic cells is a key regulator of the IFN-Ȗ,/-17 balance in atopic
dermatitis. J Allergy Clin Immunol. 2011;127:943-53
2. Vocanson M, Hennino A, Rozieres A, Poyet G, Gaillard V, Achachi A, Benetiere J, Kaiserlian D, Dubois B, Nicolas JF. ICOS is a marker for highly suppressive antigen-specific T cells sharing features of Th17/Th1
and regulatory T cells. J Allergy Clin Immunol, 2010, 126: 280-289
3. Hennino A, Vocanson M, Toussaint Y, Rodet K, Benetière J, Schmitt AM, Aries MF, Rozières A and Nicolas JF. CD8+ T cells initiate atopic dermatitis lesions. J Immunol, 2007, 178:5571-5577.
4. Akiba H, Kehren J, Ducluzeau MT, Krasteva M, Horand F, Kaiserlian D, Kaneko F, Nicolas JF. Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ TC1 cells inducing
keratinocyte apoptosis. J Immunol 2002, 168:3079-87.
5. Kehren J, Desvignes C, Krasteva M, Ducluzeau MT, Assossou O, Horand F, Hahne M, Kagi D, Kaiserlian D and Nicolas JF. Cytotoxicity is mandatory for CD8+ T cell-mediated contact hypersensitivity. J Exp
Med
, 1999, 189:779-786.
3.09-Summary team “Immunology of skin allergy and vaccination” Name: NICOLAS
First Name: Jean-François
CSS n°: 5
Unit: CIRI

Team “Immunology of skin allergy and vaccination”
Composition of the team
TEAM LEADER
PRINCIPAL
INVESTIGATORS /
SCIENTISTS
CLINICAL
RESEARCH /
TEACHING
ACTIVITIES
TECHNICAL
STUDENTS
Scientific projects
Since 1992, our studies have concerned the Skin Immune System and we have shown that the skin is an outstanding route to induce immunization but also tolerance. Our researches focus on the mechanisms of protective or pathological responses at the skin interface. Hence, two main topics are being/have been developed: i) skin allergy and ii) skin vaccination.
Axe 1: Skin allergy
1.1.Overall aim: To understand how skin allergies are initiated and develop, and to decrypt the molecular and cellular networks that promote either immunization or tolerance to allergens.
Project team “Immunology of skin allergy and vaccination” For numerous years, we have explored the mechanisms that govern the development of skin allergy, with a particular insight on two groups of T cell-mediated hypersensitivity reactions : i) contact and atopic dermatitis (eczemas), and ii) drug allergy, that comprise several diseases ranging from the frequent maculo-papulous exanthema (EMP) to the rare Toxic Epidermal necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
1.2. Project “Pathophysiology of Eczema/dermatitis and drug allergy” Contact/atopic dermatitis and drug allergy are induced through the repeated exposure of individuals to chemical (contact dermatitis, drug allergy) or protein (atopic dermatitis) allergens that are present in our daily environment. Our former works (studies/investigations) have shown that these pathologies are mediated by the infiltration and the activation of cytotoxic T cells (CTLs) into the skin. However, while contact/atopic dermatitis, as well as MPE, manifests mainly as benign and prurigineous skin eruptions, DRESS and TEN express as extended and life-threatening skin injuries. To date, why EMP/DRESS/NET patients develop such diverse clinical presentations remains an open question. Therefore, a major goal of our research is to dissect the factors that govern the severity of drug allergy. We will successively test for three different hypotheses: i) the severity of drug allergy correlates with the number, phenotype and diversity of cytotoxic lymphocytes that traffic in the blood of patients, and that are recruited at the site of drug eruptions, ii) the severity relies on intrinsic, unique and distinct functional activities of cytotoxic lymphocytes, iii) the skin and/or the infectious microenvironment conditions the magnitude of cytolytic functions of lymphocytes.
With the creation of the CIRI, we will investigate the bi-directional relationship that links the development of skin allergy and the infectious status of the allergic patient. Notably, we will examine how a latent infection impacts the onset and severity of drug allergy, and conversely, whether/how allergen (drug) exposure can prompt a potential viral/bacterial reactivation. Indeed, DRESS is an acute systemic inflammatory disease that affects the skin, liver or kidneys, following drug uptake, and it has been reported to be associated with Herpes virus reactivation (HHV-6, EBV). The role of the virus in the severity of the pathology is probable, but remains largely unknown. DRESS patients display robust activation of drug- or virus-specific cytotoxic T cells in the blood and the skin, as well as other organs such as the liver. Hence, we will analyze the respective role of drug- and virus-specific CTLs on the development of the pathology and determine the impact of viral infection on the priming of drug-specific CTLs. All the studies will be conducted in collaboration with: i) the Allergology department of Lyon-Sud Hospital (patients); ii) the biobank “Allergobiothèque” which collects the patients’ biological samples, and iii) the drug allergy reference center for the Rhone-Alpes/Auvergne area.
Of note, two supplementary models of investigation, illustrating the onset of drug allergy in infected patients, will also be addressed: i) cystic fibrosis patients, suffering from Pseudomonas pyogenes, Staphylococcus aureus polyinfections, who frequently develop penicillin allergy ii) HCV patients who develop DRESS after Telaprevir (a specific inhibitor of a hepatitis C virus serine protease) treatment. Finally, we will establish a murine model that recapitulates the impact of drug uptake on the development of skin inflammation, in presence of viral infection/reactivation. Such models will serve as a platform to decipher the underlying molecular mechanisms.
1.4. Project « New diagnostic and therapeutic methods for skin allergic diseases» Alternatively, we will pursue our previous work on the development of new predictive approaches for the detection of allergenic chemicals, responsible for contact dermatitis or drug allergy. Along with our work on T cell responses, we will design new in vitro tests that allow the specific and sensitive detection of Bcell/mAb responses. Besides this, we will concentrate our efforts on the design and the understanding of new avenues to treat skin allergic diseases, and we will use either extracorporeal photochemotherapy, described as inhibiting the stimulatory properties of dendritic cells, or new glycolipids, that would stimulate the immunodulatory functions of NKT cells.
Axis 2: Skin Vaccination
Project team “Immunology of skin allergy and vaccination” 2.1.Overall aim: To improve vaccine efficiency using the skin as a route of administration In recent years, our team has capitalized on its expertise in skin immunization to work on the development of new vaccines delivered through the epicutanous/intradermal route (Lyon Biopole Microvax, Expand-ID and TB-Dermatest projects). In order to design optimized vaccines, we will continue to dissect the cellular and molecular networks responsible for the establishment of immune responses against pathogens, or tolerance to harmless antigens, after immunization through the skin, both in experimental (in vivo/in vitro) models and in clinics.
2.2. Project « Nanoparticles and vaccination » First, we will explore whether/how the use of nanoparticle-encapsulated vaccinal preparations proves a valuable strategy, versus the use of adjuvants, to boost the immunogenicity of vaccines (and promote potent CD4+/CD8+ cytotoxic and B cell responses). We will also analyse whether nanoparticle-encapsulated vaccines improve antigen-sparring, which remains one of the major economic concern of the vaccine industry. 2.3. Project « Prediction of vaccine immunogenicity» Next, based on our predictive in vitro approaches for the detection of contact sensitizers, we will design similar methods to evaluate the in vitro immunogenicity of vaccinal preparations. For peculiar infections, it appears more and more evident that protection correlates with a robust T cell response, notably CTLs. An in vitro method that could help to evaluate the ability of vaccinal preparations to stimulate CTL is of crucial interest. 2.4. Project « Immunosenescence and vaccination » Finally, we will focus on the establishment of immune responses in the elderly. Recently, we have identified a large cohort of over 65s/elderly persons who fail to immunize against several strains of flu vaccines, suggesting that functional defects relative to immunoscenescence prevent them from gaining protection. We will capitalize on this cohort of individuals to: i) define immunoscenescence markers, and ii) develop new vaccines that overcome the immunoscenesce-induced functional defects in the elderly. Integration to the CIRI
Grants 2006-2012
FRM (Fondation pour la Recherche Médicale) Région Rhône-Alpes (TB Dermatest projects) Project team “Immunology of skin allergy and vaccination” Name: NICOLAS
First Name: Jean-François
CSS n°: 5
Unit: CIRI

Team “Immunolgy of skin allergy and vaccination”
Publications 2006-2012
1) Original publications
Vocanson M, Saint-Mezard P, Cluzel-Tailhardat M, Benetiere J, Ducluzeau MT, Chavagnac C, Tedone R, Berard F, Kaiserlian D, Nicolas JF. CD8+ T cells are effector cells of contact dermatitis to common skin allergens in mice. J Invest Dermatol, 2006, 126:815-820 . 2.
Vocanson M, Goujon C, Chabeau G, Castelain M, Valeyrie M, Floc'h F, Maliverney C, Gard A, Nicolas JF. The Skin Allergenic Properties of Chemicals May Depend on Contaminants - Evidence from Studies on Coumarin. Int Arch Allergy Immunol. 2006, 140:231-2383.
Nancey S, Holvoet S, Graber I, Joubert G, Philippe D, Martin S, Nicolas JF, Desreumaux P, Flourie B, Kaiserlian D. CD8+ cytotoxic T cells induce relapsing colitis in normal mice.
Gastroenterology. 2006, 131:485-96.
4.
Perrin-Cocon L, Agaugue S, Coutant F, Saint-Mezard P, Guironnet-Paquet A, Nicolas JF, Andre P, Lotteau V. Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses. Vaccine. 2006, 24:1254-63. 5.
Hennino A, Vocanson M, Toussaint Y, Rodet K, Benetière J, Schmitt AM, Aries MF, Rozières A and Nicolas JF. CD8+ T cells initiate atopic dermatitis lesions. J Immunol, 2007, 178:5571-5577. 6.
Bonneville M, Chavagnac C, Vocanson M, Rozieres A, Benetiere J, Pernet I, Denis A, Nicolas JF, Hennino A. Skin Contact Irritation Conditions the Development and Severity of Allergic Contact Dermatitis.,J Invest Dermatol. 2007, 127:1430-7. 7.
Caboni S, Gunera-Saad N, Ktiouet-Abassi S, Bérard F, Nicolas JF. Esomeprazole-induced DRESS syndrome. Studies of cross-reactivities among proton-pump inhibitor drugs. Allergy, 2007 Nov;62(11):1342-3. 8.
Etchart N, Hennino A, Friede M, Dahel K, Dupouy M, Goujon-Henry C, Nicolas JF, Kaiserlian D. Safety and efficacy of transcutaneous vaccination using a patch with the live-attenuated measles vaccine in humans. Vaccine, 2007; 25: 6891-99. 9.
Laurent A, Mistretta F, Bottigioli D, Dahel K, Goujon C, Nicolas JF, Hennino A, Laurent PE. Echographic measurement of skin thickness in adults by high frequency ultrasound to assess the appropriate micro needle length for intradermal delivery of vaccines. Vaccine, 2007, 25:6423-30. 10.
Hennino A, Cornu C, Rozieres A, Augey F, Villard-Truc F, Payot F, Lachaux A, Nicolas JF, Horvat B. Influence of measles vaccination on the progression of atopic dermatitis in infants. Pediatr Allergy Immunol, 2007;18:385-90. 11.
Vocanson M, Cluzel-Tailhardat M, Poyet G, Valeyrie M, Chavagnac C, Levarlet B, Courtellemont P, Rozières A, Hennino A, Nicolas JF. Depletion of human peripheral blood lymphocytes in CD25+ cells allows for the sensitive in vitro screening of contact allergens. J Invest Dermatol. 2008;128:2119-22. 12.
Lass C, Vocanson M, Wagner S, Schempp CM, Nicolas JF, Merfort I, Martin S. Anti- inflammatory and immune regulatory mechanisms prevent contact hypersensitivity to Arnica Montana L. Exp Dermatol. 2008;17:849-57. 13.
Rozieres A, Hennino A, Rodet K, Gutowski MC, Guillot I, Berard F, Cozon G, Bienvenu J, Nicolas JF. Detection and quantification of drug-specific T cells in penicillin allergy. Allergy, 2009, 64: 534-42. 3.08-Publications team “Immunology of skin allergy and vaccination” Vocanson M, Hennino A, Rozières A, Cluzel-Tailhardat M, Poyet G, Valeyrie M, Bénetière J, Tédone R, Kaiserlian D, Nicolas JF. Skin Exposure to Weak and Moderate Contact Allergens Induces IFNgamma Production by Lymph Node Cells of CD4+ T-Cell-Depleted Mice. J Invest Dermatol. 2009, 129:1185-91. 15.
Mbitikon-Kobo FM, Vocanson M, Michallet MC, Tomkowiak M, Cottalorda A, Angelov GS, Coupet CA, Djebali S, Marçais A, Dubois B, Bonnefoy-Bérard N, Nicolas JF, Arpin C, Marvel J. Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions. J Immunol. 2009;182:3846-54. 16.
Vocanson M, Hennino A, Rozieres A, Poyet G, Gaillard V, Achachi A, Benetiere J, Kaiserlian D, Dubois B, Nicolas JF. Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of Th17/Th1 and regulatory T cells. J Allergy Clin Immunol, 2010, 126: 280-289. 17.
Rozieres A, Vocanson M, Rodet K, Benetiere J, Bienvenu J, Berard F, Hennino A, Nicolas JF. CD8+ T cells mediate skin allergy to amoxicillin in a mouse model. Allergy, 2010;65:996-1003 18.
Morelon E, Pouteil-Noble C, Daoud S, Cahen R, Touraine JL, Goujon-Henry C, Weber F, Laurent P, Kaiserlian D, Nicolas JF. Immunogenicity and safety of intradermal influenza vaccination in renal transplant patients who were non-responders to conventional influenza vaccination. Vaccine, 2010, 28: 6885-90.
19.
Hennino A, Jean-Decoster C, Giordano-Labadie F, Debeer S, Vanbervliet B, Rozières A, Schmitt AM, Nicolas JF. CD8(+) T cells are recruited early to allergen exposure sites in atopy patch test reactions in human atopic dermatitis. J Allergy Clin Immunol, 2011,127:1064-7. 20.
Vanbervliet B, Akdis M, Vocanson M, Rozières A, Benetière J, Rouzaire P, Akdis CA, Nicolas JF, Hennino A. Histamine receptor H1 signaling on dendritic cells plays a key role in the IFN-?/IL-17 balance in T cell-mediated skin inflammation. J Allergy Clin Immunol, 2011,127:943-53 21.
Baeck M, Chemelle JA, Goossens A, Nicolas JF, Terreux R. Corticosteroid cross-reactivity: clinical and molecular modelling tools. Allergy, 2011, 66:1367-74. 22.
Rouzaire P, Luci C, Blasco E, Bienvenu J, Walzer T, Nicolas JF, Hennino A. Natural Killer cells and T cells induce different types of skin reactions during recall responses to haptens. Eur J Immunol. 2011 Oct 4. doi: 10.1002/eji.201141820. 23.
Vanbervliet B, Tourdot S, Mascarell L, Rouzaire P, Vocanson M, Rozières A, Benetière J, Moingeon P, Nicolas JF, Hennino A. SLIT Prevents the Development of Eczema in Percutaneous Allergen-Sensitized Mice. J Invest Dermatol. 2011 Sep 8. doi: 10.1038/jid.2011.278. [Epub ahead of print]24.
Kanjarawi R, Dercamp C, Etchart N, Adel-Patient K, Nicolas JF, Dubois B, Kaiserlian D. Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice. Int Arch Allergy Immunol, 2011, 156(4):387-396. 25.
Ploin D, Schwarzenbach F, Dubray C, Nicolas JF, Goujon C, Trong MD, Laurent PE. Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children. Vaccine, 2011, 29(46):8438-42. 26.
Soria A, Baeck M, Goossens A, Marot L, Duveille V, Derouaux AS, Nicolas JF, Tennstedt D. Patch, prick or intradermal tests to detect delayed hypersensitivity to corticosteroids? Contact Dermatitis. 2011;64:313-24. Clinical publications
1.
Goujon C, Berard F, Dahel K, Guillot I, Hennino A, Nosbaum A, Saad N, Nicolas JF. Methotrexate for the treatment of adult atopic dermatitis. Eur J Dermatol. 2006, 16:155-8. Bensaid B, Rozieres A, Berard F, Bienvenu J, Nicolas JF. IgE-mediated allergy to pristinamycin: the value of skin tests and basophil activation tests. Allergy. 2009 Nov;64(11):1694. 3.08-Publications team “Immunology of skin allergy and vaccination” Paccalin M, Weinberger B, Nicolas JF, Van Damme P, Mégard Y. The intradermal vaccination route – an attractive opportunity for influenza vaccination in the elderly. Eur Geriatr Med, 2010 Ben Said B, Berard F, Bienvenu J, Nicolas JF, Rozieres A. Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy to quinolones. Allergy, 2010;65:535-6. Ben Said B, Leray V, Nicolas JF, Rozieres A, Berard F. Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil activation test. Allergy, 2010;65:531-2. Goujon C, Dahel K, Bérard F, Guillot I, Gunera-Saad N, Nicolas JF. Autoimmune hepatitis in two psoriasis patients treated with inflixmab. J Am Acad Dermatol, 2010;63:43-4. Said BB, Kanitakis J, Graber I, Nicolas JF, Saurin JC, Berard F. Pityriasis lichenoides chronica induced by adalimumab therapy for Crohn's disease: Report of 2 cases successfully treated with methotrexate. Inflamm Bowel Dis. Inflamm Bowel Dis. 2010;16:912-3. Ben Said B, Kanitakis J, Graber I, Berard F, Nicolas JF, Saurin JC, Augey F. Severe sporotrichoid fishtank granuloma following infliximab therapy for Crohn's disease. Inflamm Bowel Dis. 2010;16:375-6. Goujon C, Gormand F, Gunera-Saad N, Dahel K, Vial T, Nicolas JF. [The relevance of diagnostic criteria for latent tuberculosis before initiation of TNF-alpha inhibitors in psoriasis patients] Ann Dermatol Venereol. 2010;137:437-43. Nosbaum A, Rozières A, Ben Said B, Nicolas JF, Bérard F. [Glycopeptide-induced cutaneous adverse Said BB, Rozieres A, Martin O, Nicolas JF, Berard F. Severe hypocalcemia and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome under deferasirox therapy for myelodysplasic syndrome. Am J Hematol. 2011 Oct 20. Nosbaum A, Pecquet C, Bayrou O, Amsler E, Nicolas JF, Bérard F, Francès C. Treatment with propranolol of 6 patients with idiopathic aquagenic pruritus. J Allergy Clin Immunol. 2011 May 24. Augey F, Gunera-Saad N, Bensaid B, Nosbaum A, Berard F, Nicolas JF. Chronic spontaneous urticaria is not an allergic disease. Eur J Dermatol. 2011, 21:349-53. Nosbaum A, Ben Said B, Halpern SJ, Nicolas JF, Bérard F. Systemic allergic contact dermatitis to black cumin essential oil expressing as generalized erythema multiforme. Eur J Dermatol. 2011, 21:447-8. Augey F, Nosbaum A, Berard F, Nicolas JF. Corticosteroids should not be used in urticaria because of the potential risk of steroid dependence and development of severe anti-H1- resistant urticaria. Eur J Dermatol. 2011, 21:431. Augey F, Nosbaum A, Ben-Said B, Bérard F, Nicolas JF. [Chronic urticaria and corticodependence: corticosteroids have no role in the treatment of urticaria]. Ann Dermatol Venereol. 2011;138:3-4. 3.08-Publications team “Immunology of skin allergy and vaccination” 2) Reviews
Hennino A, Bérard F, Guillot I, Saad N, Rozières A, Nicolas JF. Pathophysiology of Urticaria. Clin Rev Allergy Immunol. 2006 Feb;30(1):3-12. 2.
Vocanson M, Hennino A, Chavagnac C, Rozières A, Saint-Mezard P, Akiba H, Satoh M, Kaiserlian D, Nicolas JF. Eczéma allergique de contact - Comment ré-induire une tolérance ? Med Sci (Paris). 2006 Feb;22(2):158-163 3.
Nicolas JF, Guy B. Intradermal, epidermal and transcutaneous vaccination, from immunology to clinical practice. Expert Rev Vaccines. 2008;7:1201-14. Review. 4.
Vocanson M, Hennino A, Rozières A, Poyet G, Nicolas JF. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy. 2009;64:1699-714 5.
Rozieres A, Vocanson M, Bensaïd B, Nosbaum A, Nicolas JF. Role of T cells in nonimmediate allergic drug reactions. Curr Opin Allergy Clin Immunol. 2009;9:305-10. 6.
Baeck M, Marot L, Nicolas JF, Pilette C, Tennstedt D, Goossens A. Allergic hypersensitivity to topical and systemic corticosteroids: a review. Allergy. 2009 Mar 27. 7.
Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF. Allergic and irritant contact dermatitis. Eur J Dermatol. 2009;19:325-32.
8.
Martin SF, Esser PR, Schmucker S, Dietz L, Naisbitt DJ, Park BK, Vocanson M, Nicolas JF, Keller M, Pichler WJ, Peiser M, Luch A, Wanner R, Maggi E, Cavani A, Rustemeyer T, Richter A, Thierse HJ, Sallusto F. T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays. Cell Mol Life Sci. 2010, 67(24):4171-84. 9.
Nosbaum A, Hennino A, Berard F, Nicolas JF. Patch testing in atopic dermatitis patients. Eur J Dermatol. 2010;20:563-6. Nosbaum A, Augey F, Nicolas JF, Bérard F.[Pathophysiology of urticaria and therapeutic approaches] Rev Med Interne. 2010;31 Suppl 1:S18-22. 10.
Roujeau JC, Bricard G, Nicolas JF. Drug-induced epidermal necrolysis: Important new piece to end the puzzle. J Allergy Clin Immunol, 2011,128(6):1277-8 11.
Augey F, Nicolas JF, Doutre MS, Amsler E, Mathelier-Fusade P, Lambert C, Martinage C, Nosbaum A. [Why a "urticaria" group of the French dermatological society?]. Ann Dermatol Venereol. 2011;138:281-3. 3) Books and chapters
Mirabelle S, Rozieres A, Nosbaum A, Bérard F, Nicolas JF. Immunosénescence systémique et cutanée in “ In « Progrès en dermato-allergologie », John Libbey Eurotext, Montrouge, France, 2010. 4) Others
Nicolas JF. Jean Thivolet. Eur J Dermatol. 2011, 21(2):155. Nicolas JF. Jean Thivolet (1926-2011). J Invest Dermatol. 2011;131:1400. 3.08-Publications team “Immunology of skin allergy and vaccination” Name: NICOLAS
First Name: Jean-François
CSS n°: 5
Unit: CIRI

Curriculum
NICOLAS Jean François, M.D, Ph.D.,
Date de naissance : 25 mai 1955
Situation familiale: Marié, 2 enfants
Situation professionnelle actuelle: CNU 47-03
Professeur des Universités - Praticien Hospitalier
Immunologie Clinique - Dermatologue
(N° COM : 69/07496 ; RPPS : 10003043543 ; N°ADELI : 691074967)
Adresse professionnelle Universitaire: Inserm U 851, Responsable Equipe 9,
Tour Pasteur, 21 av. Tony Garnier, F- 69365 Lyon Cx 07
Tel: 04 37 28 23 48; Fax: 04 37 28 23 41; Mel: jean-francois.nicolas@inserm.fr
Adresse professionnelle Hospitalière: Service Allergologie et Immunologie Clinique,
Pavillon Dufourt - 5F, Centre Hospitalier Lyon-Sud, F-69495 Pierre-Bénite Cedex
Tel: 04 78 86 15 72; Fax: 04 78 86 15 28; Mel: jean-francois.nicolas@chu.lyon.fr
Fonctions universitaires – Professeur d’Immunologie UFR Lyon-Sud, Université Lyon1
Enseignant d’immunologie UFR Lyon-Sud, Université Claude Bernard Lyon1
Membre du CNU section 47-03
DESC Allergologie et Immunologie Clinique - Coordonnateur interrégional Rhone-Alpes-Auvergne
Fonctions recherche - Responsable d’équipe INSERM
Unité 851 « Immunité, infection, vaccination », IFR Biosciences Lyon-Gerland 128
Fonctions hospitalières – Praticien Hospitalier Hospices Civils de Lyon, CH Lyon-Sud
Responsable de la recherche dans le service « Allergologie et Immunologie Clinique », CH Lyon-Sud
Centre de Compétences Inter-régional Rhone-Alpes-Auvergne « Dermatoses bulleuses toxiques-Allergies aux
médicaments » - Coordonnateur
TITRES UNIVERSITAIRES
- Doctorat en Médecine, UFR Grange-Blanche
- Certificat d'Études Spéciales de Dermatologie - Diplome d'Études et de Recherches en Biologie Humaine, Lyon I - Chef de Clinique (Clinique Dermatologie, Hop E Herriot) - Diplome de Doctorat, Université Cl. Bernard, Lyon I - Chercheur Poste Accueil INSERM Inserm Unité 209 - Directeur de Recherche INSERM U209, U346 et U80 - Habilitation à Diriger des Recherches UCBLyon I - Professeur des Universités (Immunologie Clinique) - Praticien hospitalier TITRES HOSPITALIERS ET FONCTIONS DE SOINS
- Internat des Hopitaux de Lyon
- Praticien Hospitalier (Immunologie Clinique et Allergologie) PRINCIPALES RESPONSABILITES SCIENTIFIQUES ET ADMINISTRATIVES

Responsable d’équipe INSERM (équipe 8 INSERM U 851) Chef de service adjoint « Service d’Allergologie et Immunologie Clinique », CH Lyon-Sud Rhone-Alpes du DESC Allergologie et Immunologie Clinique (2004-2009) Coordonnateur du Centre de Compétences Inter-régional « Allergies aux médicaments », CH Lyon-Sud Membre du collège des enseignants d’immunologie (ASSIM) et de dermatologie (CED) 3.10-CV team leader“Immunology of skin allergy and vaccination” Membre de Sociétés savantes nationales et européenes Immunologie, Allergologie et Dermatologie Membre du conseil d’administration de la Société Française d’Allergie Président du Conseil Scientifique de la Société Française d’Allergie Membre de la commisssion de formation ARIIS Expert des conférences de consensus en Dermatologie (mélanome, urticaire, dermatite atopique) Rédacteur en chef du journal "European Journal of Dermatology" Responsable scientifique du site « www.allergolyon.org » Directeur de thèse Ph.D
Jean-Luc Garrigue, MD, PhD – 1990-93 – Chercheur L’Oréal depuis 1995, Paris ; Hélène Bour, PhD – 1991-94 –
Senior scientist depuis 1998, laboratoire J Blustone, USA ; Maya Krasteva, MD, PhD – 1994-98 – Médecin-
chercheur L’Oreal depuis 2002, Paris ; Eric Peyron, MD, PhD – 1995-99 – Psychiatre, installe en clinique depuis
1999 ; Jeanne Kehren, Vétérinaire – 1995-99 – Chercheur Novartis (2000-2009), Sanofi-Aventis (depuis 2009) ;
Pierre Saint-Mezard, Scientifique – 1998-2002 – Chercheur Novartis, Bale depuis 2004 ; Sophie Bosset-Saint-
Mezard, Vétérinaire – 1999-2003- Chercheur Novartis, Bale depuis 2004 ; Magali Thaillardat, Scientifique – 2002-
2006 - Chercheur LVMH/C.Dior depuis 2007 ; Marlene Bonneville, Scientifique – 2003- 2006 – Chercheur sanofi-
pasteur depuis 2007 ; Aurore Rozieres, Scientifique – 2002-2007 – Assitante Hospitalo-Universitaire CHU Lyon ;
Marc Vocanson, Scientifique- 2004-2008 – Ingenieur Université Lyon1 ; Hélène Perrin, Scientifique – 2006-2009 –
Post-Doc ; Julie-Anne Chemelle –Pharmacienne – 2007-2011 – Post-Doc ; Audrey Nosbaum – Médecin – 2007 –
en cours ; Paul Rouzaire – Pharmacien – 2009 - en cours
SELECTION DE PUBLICATIONS
-
Vanbervliet B, Akdis M, Vocanson M, Rozières A, Benetière J, Rouzaire P, Akdis C, Nicolas JF, Hennino A.
Histamine receptor H1 signaling on dendritic cells is a key regulator of the IFN-J/IL-17 balance in atopic dermatitis.
J Allergy Clin Immunol. 2011;127:943-53
- Vocanson M, Hennino A, Rozieres A, Poyet G, Gaillard V, Achachi A, Benetiere J, Kaiserlian D, Dubois B,
Nicolas JF. ICOS is a marker for highly suppressive antigen-specific T cells sharing features of Th17/Th1 and
regulatory T cells. J Allergy Clin Immunol, 2010, 126: 280-289
- Rozieres A, Vocanson M, Bensaïd B, Nosbaum A, Nicolas JF. Role of T cells in nonimmediate allergic drug
reactions. Curr Opin Allergy Clin Immunol. 2009;9:305-10.
- Vocanson M, Hennino A, Rozières A, Poyet G, Nicolas JF. Effector and regulatory mechanisms in allergic contact
dermatitis. Allergy. 2009;64:1699-714
- Rozieres A, Hennino A, Rodet K, Gutowski MC, Guillot I, Berard F, Cozon G, Bienvenu J, Nicolas JF. Detection
and quantification of drug-specific T cells in penicillin allergy. Allergy, 2009, 64: 534-42.
- Hennino A, Vocanson M, Toussaint Y, Rodet K, Benetière J, Schmitt AM, Aries MF, Rozières A and Nicolas JF.
CD8+ T cells initiate atopic dermatitis lesions. J Immunol, 2007, 178:5571-5577.
- Saint-Mezard P, Chavagnac C, Bosset S, Ionescu M, Peyron E, Kaiserlian D, Nicolas JF, Berard F. Psychological
Stress Exerts an Adjuvant Effect on Skin Dendritic Cell Functions In Vivo. J Immunol. 2003 Oct 15;171(8):4073-
4080.
- Akiba H, Kehren J, Ducluzeau MT, Krasteva M, Horand F, Kaiserlian D, Kaneko F, Nicolas JF. Skin
inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ TC1 cells inducing
keratinocyte apoptosis. J Immunol 2002, 168:3079-87.
- Kehren J, Desvignes C, Krasteva M, Ducluzeau MT, Assossou O, Horand F, Hahne M, Kagi D, Kaiserlian D and
Nicolas JF. Cytotoxicity is mandatory for CD8+ T cell-mediated contact hypersensitivity. J Exp Med, 1999,
189:779-786.
- Krasteva M, Kehren J, Horand F, Akiba H, Choquet G, Ducluzeau MT, Tedone R, Garrigue JL, Kaiserlian D,
Nicolas JF. Dual role of dendritic cells in the induction and the down-regulation of antigen-specific cutaneous
inflammation. J Immunol, 1998, 160:1181-1190.
- Bour H, Peyron E, Desvignes C, Kaiserlian D, Revillard JP, Nicolas JF. MHC class I-restricted CD8+T cells and
MHC class II-restricted CD4+Tcells respectively mediate and regulate contact sensitivity to DNFB. Eur J
Immunol, 1995,
25:3006-3010.
3.10-CV team leader“Immunology of skin allergy and vaccination”

Source: http://www.ifr128.prd.fr/Nicolas/Images/CIRI_Team_14.pdf

kingdomvision.co.za

ARMAGEDDON, GOG AND MAGOG Orlando Mostert Kingdomvision.co.za INTRODUCTION The common view in all popular prophecy books is that the great “end time” battle of Armageddon described in Revelations and in Ezekiel 38 and 39 is a coming invasion of Israel by a coalition of Arab armies led by Russia out of the north. This is totally false. There is no Russian invasion of Israel coming.

Continuous bronchodilator therapy during mechanical ventilation

New Technology Offers New Opportunities: Continuous Bronchodilator Therapy Key words: aerosol, ventilator, nebulizer, pMDI, DPI Mr. Fink was previously an employee of Aerogen, Inc., and involved in the development of the Aeroneb vibrating mesh technology and its use in critical care Introduction Patients with severe exacerbations of asthma, refractory to standard dose and frequency of inh

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