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Transplantations and osteoimmonology

The interest of the group are divided between clinical research that concerns follow-up of patients after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), i.e liver, kidney and pancreas/islets, and more basic research in the field of transplant immunology. Due to close contact with the service of haematology (Prof Passweg, Dr Kindler), the service of Nephrology (Prof. Martin, Dr Hadaya), and the service of transplantation (Profs Mentha, Morel, Buhler and Berney) we have an access to patient samples and we also serve as repository for cells and DNA samples of transplanted patients. Our main research project is focused on natural killer cells (NK cells). These cells make the link between innate and adaptative immunity and are implied in anti-tumoral and anti-viral responses. Additionally, they also seem to play a role in the immune responseżs regulation. In SOT, NK cells are implied in the anti-viral response, which is particularly important since the patients are under high doses of immunosuppressive treatments with lymphocytes T as principal targets. As NK cells express a complex network of receptors, the group is interested in analyzing the genetic influence of these receptors on the immune response after SOT and also HSCT. Furthermore, NK cells were showed to play a major role in the graft effect against leukaemia in haematopoietic stem cell transplantation. The group is interested in amplifying to a wide scale these NK cells ex vivo with cytokines in order to reinfuse them into the patients. We also developed close collaboration with the Service of Hematology to analyse the influence of mesenchymal cells which seems to have an important immunomodulatory activity on NK cells. Finally, thanks to a long lasting active collaboration with the Division of Bone and Mineral Metabolism (Prof. Ferrari) we have an interest in osteoimmunology by analysing the influence of the proinflammatory cytokines IL-15 and IL-21 on T lymphocytes and NK cells on bone loss in primary and secondary bone remodelling animal models as well as in vitro assays, studying the interplay between immune and bone cells.
Our national collaboration include the żréseau romand de transplantation with le CHUVż (Prof. Pascual, Dr V. Aubert), the network of the Swiss University Hospital which have a programme of HSTC or SOT and at the international with the Transplant Biology Resesearch Center, Massachusets General Hospital (Pr. M. Sykes and D: Sachs) et the Beth Israel hospital (Pr. T. Strom), both in Boston, MA.

Group's publications

Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark.
AMERICAN JOURNAL OF TRANSPLANTATION
2009 vol. 9(2) pp. 419-423
BERNEY T, FERRARI-LACRAZ SYLVIE, BUEHLER LH, OBERHOLZER J, MARANGON NICOLA, PHILIPPE J, VILLARD J, MOREL P

Pluripotent stem cells as new drugs? The example of Parkinson's disease
INTERNATIONAL JOURNAL OF PHARMACEUTICS
2009 vol. 381(2) pp. 113-121
PREYNAT-SEAUVE O, BURKHARD PR, VILLARD J, ZINGG W, GINOVART N, FEKI A, DUBOIS-DAUPHIN M, HURST S, MAURON A, JACONI M, KRAUSE KH

Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
2009 vol. 13(9B) pp. 3556-3569
PREYNAT-SEAUVE O, DE RHAM C, TIREFORT D, FERRARI-LACRAZ SYLVIE, KRAUSE KH, VILLARD J

The Transcription Factor RFX Protects MHC Class II Genes against Epigenetic Silencing by DNA Methylation
JOURNAL OF IMMUNOLOGY
2009 vol. 183(4) pp. 2545-2553
SEGUIN-ESTEVEZ Q, DE PALMA R, KRAWCZYK M, LEIMGRUBER E, VILLARD J, PICARD C, TAGLIAMACCO A, ABBATE G, GORSKI J, NOCERA A, REITH W

Sequence of a novel HLA-A2 allele in a haematopoietic stem cell donor of the international registry.
TISSUE ANTIGENS
2009 vol. 74(3) pp. 248-249
KERVAIRE B, SCHMIDT AH, VILLARD J, TIERCY JM

Humoral and cellular rejection after combined liver-kidney transplantation in low immunologic risk recipients
TRANSPLANT INTERNATIONAL
2009 vol. 22(2) pp. 242-246
HADAYA K, FERRARI-LACRAZ SYLVIE, GIOSTRA E, MAJNO P, MOLL S, RUBBIA-BRANDT L, MARANGON NICOLA, VENETZ JP, BOLLE JF, MENTHA G, VILLARD J

In vivo investigations on anti-fibrotic potential of proteasome inhibition in lung and skin fibrosis.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
2008 vol. 39(4) pp. 458-465
FINESCHI S, BONGIOVANNI MASSIMO, DONATI Y, DJAAFAR S, NASO F, GOFFIN L, ARGIROFFO CB, PACHE JC, DAYER JM, FERRARI-LACRAZ SYLVIE, CHIZZOLINI C

Natural killer cell receptor repertoire and their ligands, and the risk of CMV infection after kidney transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
2008 vol. 8(12) pp. 2674-2683
HADAYA K, DE RHAM C, BANDELIER C, BANDELIER CH, FERRARI-LACRAZ SYLVIE, JENDLY S, BERNEY T, BUHLER L, KAISER L, SEEBACH J, TIERCY JM, MARTIN PY, VILLARD J

Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion.
BLOOD
2008 vol. 112(9) pp. 3696-3703
CHIZZOLINI C, CHICHEPORTICHE R, ALVAREZ M, DE RHAM C, ROUX-LOMBARD P, FERRARI-LACRAZ SYLVIE, DAYER JM

IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes.
INTERNATIONAL IMMUNOLOGY
2008 vol. 20(8) pp. 1009-1018
FERRARI-LACRAZ SYLVIE, CHICHEPORTICHE R, SCHNEITER G, MOLNARFI NICOLAS, VILLARD J, DAYER JM

Human herpesvirus-6 variant A encephalomyelitis.
NEUROLOGY
2008 vol. 70(12) pp. 974-976
POT C, BURKHARD PR, VILLARD J, PERRIN L, KAISER L, LANDIS T, LALIVE P.H.

A new HLA-DR4 allele, DRB1*0474, with an unusual residue at position 77.
TISSUE ANTIGENS
2008 vol. 72(5) pp. 500-501
DESAULES C, VILLARD J, TIERCY JM

DNA typing by microbead arrays and PCR-SSP: apparent false-negative or -positive hybridization or amplification signals disclose new HLA-B and -DRB1 alleles.
TISSUE ANTIGENS
2008 vol. 71(3) pp. 238-241
RAHAL M, KERVAIRE B, VILLARD J, TIERCY JM

Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation.
TRANSPLANTATION
2008 vol. 86(2) pp. 357-359
FERRARI-LACRAZ SYLVIE, BERNEY T, MOREL P, MARANGON NICOLA, HADAYA K, DEMUYLDER-MISCHLER S, PONGRATZ G, PERNIN N, VILLARD J

Airway epithelial IL-15 transforms monocytes into dendritic cells
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
2007 vol. 37 pp. 75-84
REGAMEY N, OBREGON C, FERRARI-LACRAZ S, VAN LEER C, CHANSON M, NICOD LP, GEISER T

The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors.
ARTHRITIS RESEARCH & THERAPY
2007 vol. 9(6) pp. 125-125
DE RHAM C, FERRARI-LACRAZ SYLVIE, JENDLY S, SCHNEITER G, DAYER JM, VILLARD J

Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine
EXPERIMENTAL HEMATOLOGY
2007 vol. 35(7) pp. 1140-1152
SHAFFER J, VILLARD J, MEANS TK, ALEXANDER S, DOMBKOWSKI D, DEY BR, MCAFEE S, BALLEN KK, SAIDMAN S, PREFFER FI, SACHS DH, SPITZER TR, SYKES M

Investigation of alloreactive NK cells in mixed lymphocyte reactions using paraformaldehyde-silenced target cells
JOURNAL OF IMMUNOLOGICAL METHODS
2007 vol. 321 pp. 196-199
ZENHAEUSERN G, GASSER O, SALEH L, VILLARD J, TIERCY JM, HESS C

Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab
TRANSPLANT INTERNATIONAL
2007 vol. 20 pp. 102-105
HRISTEA, D, HADAYA, K, MARANGON, N, BUHLER, L, VILLARD, J, MOREL, P, MARTIN, PY

Acute humoral rejection in kidney allograft following a third-party arterial transplantation
AMERICAN JOURNAL OF TRANSPLANTATION
2006 vol. 6 pp. 3038-3039
FERRARI-LACRAZ S, BERNEY T, BEDNARKEWICZ M, BINET I, TIERCY JM, MARTIN PY, VILLARD J

Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications
BLOOD
2006 vol. 07(1) pp. 389-396
CHALANDON Y. ET AL.

Immunologic monitoring: what's new?
REVUE MÉDICALE SUISSE
2006 vol. 2(62) pp. 1034-1041
FERRARI-LACRAZ SYLVIE, VILLARD JEAN

Anti-HLA antibody repertoire after IVIg infusion in highly sensitised patients waiting for kidney transplantation
SWISS MEDICAL WEEKLY
2006 vol. 136 pp. 696-702
FERRARI-LACRAZ S, AUBERT V, BUHLER L, PASCUAL M, ANDRESEN I, BINET I, MARTIN PY, VILLARD J

Immunity after organ transplantation
SWISS MEDICAL WEEKLY
2006 vol. 136 pp. 71-77
VILLARD J

CD8(+) T cells resistant to costimulatory blockade are controlled by an antagonist interleukin-15/Fc protein
TRANSPLANTATION
2006 vol. 82 pp. 1510-1517
FERRARI-LACRAZ S, ZHENG XX, FUEYO AS, MASLINSKI W, MOLL T, STROM TB

Immunité cellulaire: les leçons de la transplantation de moelle osseuse allogénique (TMO)
MEDECINE ET HYGIENE : JOURNAL SUISSE D'INFORMATIONS MEDICALES
2002 vol. 60 pp. 395-399
VILLARD J, CHAPUIS B, HELG C, ROOSNEK E

Direct Genetic Correction as a New Method for Diagnosis and Molecular Characterization of MHC Class II Deficiency
MOLECULAR THERAPY
2002 vol. 6 pp. 824-829
MATHEUX F, AYDAN IKINCIOGULLARI, DAVID A. ZAPATA, BARRAS E, ZUFFEREY M, FIGEN DOGU, JOSÉ R. REGUEIRO, REITH W, VILLARD J

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL BIOLOGY RESEARCH

J.VILLARD - S. FERRARI-LACRAZ	Head of group CV	Research subject	Members of the group


	Links about the group J. Villard - S. Ferrari-Lacraz HUG/Spécialités de Médecine Serv Immunologie Allergologie Rue Gabrielle-Perret-Gentil 4 1211 Genève 14 Suisse jean.villard@hcuge.ch Tel.: 022/372.93.94 Fax: 022/372.93.90 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Transplantations and osteoimmonology The interest of the group are divided between clinical research that concerns follow-up of patients after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), i.e liver, kidney and pancreas/islets, and more basic research in the field of transplant immunology. Due to close contact with the service of haematology (Prof Passweg, Dr Kindler), the service of Nephrology (Prof. Martin, Dr Hadaya), and the service of transplantation (Profs Mentha, Morel, Buhler and Berney) we have an access to patient samples and we also serve as repository for cells and DNA samples of transplanted patients. Our main research project is focused on natural killer cells (NK cells). These cells make the link between innate and adaptative immunity and are implied in anti-tumoral and anti-viral responses. Additionally, they also seem to play a role in the immune responseżs regulation. In SOT, NK cells are implied in the anti-viral response, which is particularly important since the patients are under high doses of immunosuppressive treatments with lymphocytes T as principal targets. As NK cells express a complex network of receptors, the group is interested in analyzing the genetic influence of these receptors on the immune response after SOT and also HSCT. Furthermore, NK cells were showed to play a major role in the graft effect against leukaemia in haematopoietic stem cell transplantation. The group is interested in amplifying to a wide scale these NK cells ex vivo with cytokines in order to reinfuse them into the patients. We also developed close collaboration with the Service of Hematology to analyse the influence of mesenchymal cells which seems to have an important immunomodulatory activity on NK cells. Finally, thanks to a long lasting active collaboration with the Division of Bone and Mineral Metabolism (Prof. Ferrari) we have an interest in osteoimmunology by analysing the influence of the proinflammatory cytokines IL-15 and IL-21 on T lymphocytes and NK cells on bone loss in primary and secondary bone remodelling animal models as well as in vitro assays, studying the interplay between immune and bone cells. Our national collaboration include the żréseau romand de transplantation with le CHUVż (Prof. Pascual, Dr V. Aubert), the network of the Swiss University Hospital which have a programme of HSTC or SOT and at the international with the Transplant Biology Resesearch Center, Massachusets General Hospital (Pr. M. Sykes and D: Sachs) et the Beth Israel hospital (Pr. T. Strom), both in Boston, MA. Group's publications Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark. AMERICAN JOURNAL OF TRANSPLANTATION 2009 vol. 9(2) pp. 419-423 BERNEY T, FERRARI-LACRAZ SYLVIE, BUEHLER LH, OBERHOLZER J, MARANGON NICOLA, PHILIPPE J, VILLARD J, MOREL P Pluripotent stem cells as new drugs? The example of Parkinson's disease INTERNATIONAL JOURNAL OF PHARMACEUTICS 2009 vol. 381(2) pp. 113-121 PREYNAT-SEAUVE O, BURKHARD PR, VILLARD J, ZINGG W, GINOVART N, FEKI A, DUBOIS-DAUPHIN M, HURST S, MAURON A, JACONI M, KRAUSE KH Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 2009 vol. 13(9B) pp. 3556-3569 PREYNAT-SEAUVE O, DE RHAM C, TIREFORT D, FERRARI-LACRAZ SYLVIE, KRAUSE KH, VILLARD J The Transcription Factor RFX Protects MHC Class II Genes against Epigenetic Silencing by DNA Methylation JOURNAL OF IMMUNOLOGY 2009 vol. 183(4) pp. 2545-2553 SEGUIN-ESTEVEZ Q, DE PALMA R, KRAWCZYK M, LEIMGRUBER E, VILLARD J, PICARD C, TAGLIAMACCO A, ABBATE G, GORSKI J, NOCERA A, REITH W Sequence of a novel HLA-A2 allele in a haematopoietic stem cell donor of the international registry. TISSUE ANTIGENS 2009 vol. 74(3) pp. 248-249 KERVAIRE B, SCHMIDT AH, VILLARD J, TIERCY JM Humoral and cellular rejection after combined liver-kidney transplantation in low immunologic risk recipients TRANSPLANT INTERNATIONAL 2009 vol. 22(2) pp. 242-246 HADAYA K, FERRARI-LACRAZ SYLVIE, GIOSTRA E, MAJNO P, MOLL S, RUBBIA-BRANDT L, MARANGON NICOLA, VENETZ JP, BOLLE JF, MENTHA G, VILLARD J In vivo investigations on anti-fibrotic potential of proteasome inhibition in lung and skin fibrosis. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 2008 vol. 39(4) pp. 458-465 FINESCHI S, BONGIOVANNI MASSIMO, DONATI Y, DJAAFAR S, NASO F, GOFFIN L, ARGIROFFO CB, PACHE JC, DAYER JM, FERRARI-LACRAZ SYLVIE, CHIZZOLINI C Natural killer cell receptor repertoire and their ligands, and the risk of CMV infection after kidney transplantation. AMERICAN JOURNAL OF TRANSPLANTATION 2008 vol. 8(12) pp. 2674-2683 HADAYA K, DE RHAM C, BANDELIER C, BANDELIER CH, FERRARI-LACRAZ SYLVIE, JENDLY S, BERNEY T, BUHLER L, KAISER L, SEEBACH J, TIERCY JM, MARTIN PY, VILLARD J Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. BLOOD 2008 vol. 112(9) pp. 3696-3703 CHIZZOLINI C, CHICHEPORTICHE R, ALVAREZ M, DE RHAM C, ROUX-LOMBARD P, FERRARI-LACRAZ SYLVIE, DAYER JM IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes. INTERNATIONAL IMMUNOLOGY 2008 vol. 20(8) pp. 1009-1018 FERRARI-LACRAZ SYLVIE, CHICHEPORTICHE R, SCHNEITER G, MOLNARFI NICOLAS, VILLARD J, DAYER JM Human herpesvirus-6 variant A encephalomyelitis. NEUROLOGY 2008 vol. 70(12) pp. 974-976 POT C, BURKHARD PR, VILLARD J, PERRIN L, KAISER L, LANDIS T, LALIVE P.H. A new HLA-DR4 allele, DRB1*0474, with an unusual residue at position 77. TISSUE ANTIGENS 2008 vol. 72(5) pp. 500-501 DESAULES C, VILLARD J, TIERCY JM DNA typing by microbead arrays and PCR-SSP: apparent false-negative or -positive hybridization or amplification signals disclose new HLA-B and -DRB1 alleles. TISSUE ANTIGENS 2008 vol. 71(3) pp. 238-241 RAHAL M, KERVAIRE B, VILLARD J, TIERCY JM Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation. TRANSPLANTATION 2008 vol. 86(2) pp. 357-359 FERRARI-LACRAZ SYLVIE, BERNEY T, MOREL P, MARANGON NICOLA, HADAYA K, DEMUYLDER-MISCHLER S, PONGRATZ G, PERNIN N, VILLARD J Airway epithelial IL-15 transforms monocytes into dendritic cells AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 2007 vol. 37 pp. 75-84 REGAMEY N, OBREGON C, FERRARI-LACRAZ S, VAN LEER C, CHANSON M, NICOD LP, GEISER T The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors. ARTHRITIS RESEARCH & THERAPY 2007 vol. 9(6) pp. 125-125 DE RHAM C, FERRARI-LACRAZ SYLVIE, JENDLY S, SCHNEITER G, DAYER JM, VILLARD J Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine EXPERIMENTAL HEMATOLOGY 2007 vol. 35(7) pp. 1140-1152 SHAFFER J, VILLARD J, MEANS TK, ALEXANDER S, DOMBKOWSKI D, DEY BR, MCAFEE S, BALLEN KK, SAIDMAN S, PREFFER FI, SACHS DH, SPITZER TR, SYKES M Investigation of alloreactive NK cells in mixed lymphocyte reactions using paraformaldehyde-silenced target cells JOURNAL OF IMMUNOLOGICAL METHODS 2007 vol. 321 pp. 196-199 ZENHAEUSERN G, GASSER O, SALEH L, VILLARD J, TIERCY JM, HESS C Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab TRANSPLANT INTERNATIONAL 2007 vol. 20 pp. 102-105 HRISTEA, D, HADAYA, K, MARANGON, N, BUHLER, L, VILLARD, J, MOREL, P, MARTIN, PY Acute humoral rejection in kidney allograft following a third-party arterial transplantation AMERICAN JOURNAL OF TRANSPLANTATION 2006 vol. 6 pp. 3038-3039 FERRARI-LACRAZ S, BERNEY T, BEDNARKEWICZ M, BINET I, TIERCY JM, MARTIN PY, VILLARD J Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications BLOOD 2006 vol. 07(1) pp. 389-396 CHALANDON Y. ET AL. Immunologic monitoring: what's new? REVUE MÉDICALE SUISSE 2006 vol. 2(62) pp. 1034-1041 FERRARI-LACRAZ SYLVIE, VILLARD JEAN Anti-HLA antibody repertoire after IVIg infusion in highly sensitised patients waiting for kidney transplantation SWISS MEDICAL WEEKLY 2006 vol. 136 pp. 696-702 FERRARI-LACRAZ S, AUBERT V, BUHLER L, PASCUAL M, ANDRESEN I, BINET I, MARTIN PY, VILLARD J Immunity after organ transplantation SWISS MEDICAL WEEKLY 2006 vol. 136 pp. 71-77 VILLARD J CD8(+) T cells resistant to costimulatory blockade are controlled by an antagonist interleukin-15/Fc protein TRANSPLANTATION 2006 vol. 82 pp. 1510-1517 FERRARI-LACRAZ S, ZHENG XX, FUEYO AS, MASLINSKI W, MOLL T, STROM TB Immunité cellulaire: les leçons de la transplantation de moelle osseuse allogénique (TMO) MEDECINE ET HYGIENE : JOURNAL SUISSE D'INFORMATIONS MEDICALES 2002 vol. 60 pp. 395-399 VILLARD J, CHAPUIS B, HELG C, ROOSNEK E Direct Genetic Correction as a New Method for Diagnosis and Molecular Characterization of MHC Class II Deficiency MOLECULAR THERAPY 2002 vol. 6 pp. 824-829 MATHEUX F, AYDAN IKINCIOGULLARI, DAVID A. ZAPATA, BARRAS E, ZUFFEREY M, FIGEN DOGU, JOSÉ R. REGUEIRO, REITH W, VILLARD J Research's domains