Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome

Autor: Xi Chen, Thomas Senage, Vered Padler-Karavani, Ludmilla Le Berre, Kristina M. Harris, Rafael Mañez, Stephen E. Gitelman, Ron Amon, Milan V. Teraiya, Hoa L. Mai, Cesare Galli, Cristina Costa, Manuel Galiñanes, Jean Christian Roussel, Thi Van Ha Nguyen, Sophie Brouard, Hélène Perreault, Béatrice Charreau, Thierry Le Tourneau, Jean-Paul Soulillou, Shani Leviatan Ben-Arye, Sarah Bruneau, Emanuele Cozzi, Richard Danger, Hai Yu
Přispěvatelé: Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Department of Cell Research and Immunology, Tel Aviv University [Tel Aviv], Service de Chirurgie Cardio-Thoracique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Chemistry [Winnipeg, Manitoba, Canada], University of Manitoba [Winnipeg], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), University of California [Davis] (UC Davis), University of California, Avantea Laboratory of Reproductive Technologies [Cremona, Italy], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Intensive Care Medicine Department [Barcelona, Spain], Hospital Universitario de Bellvitge, Department of Cardiac Surgery & Reparative Therapy of the Heart [Barcelona, Spain], Vall d'Hebron University Hospital [Barcelona]-Vall d’Hebron Research Institute (VHIR), Massachusetts General Hospital [Boston], Division of Pediatric Endocrinology and Diabetes [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California, Transplantation Immunology Unit [Padua, Italy] (Department of Transfusion Medicine), University of Padua–Ospedale Giustinianeo [Padua, Italy], The European Union Seventh Framework Program (FP7/2007/2013) under the Grant agreement 603049 for Translink consortium eralitat de Catalunya (Spain) (to C.C.). Richard Danger was supported by a Marie Skłodowska‐Curie fellowship (IF‐EF) from the European U(http://www.translinkproject.com/) (to C.G., J‐C.R., R.M., X.C., C.C., M.G., E.C., V.P‐K, and J‐P.S.). This work was also supported by a grant from The Israeli Ministry of Science, Technology and Space No. 3‐14353 (to V.P‐K). This work was also supported by Ministerio de Economía y Competitividad‐ISCiii (PI15/00181), by FEDER funds, a way to build Europe, and by the PERIS program from Gennion’s Horizon 2020 research and innovation programme under the Grant Agreement No. 7062, European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Tel Aviv University (TAU), Unité de recherche de l'institut du thorax (ITX-lab), University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Università degli Studi di Padova = University of Padua (Unipd), Le Bihan, Sylvie, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID
Rok vydání: 2019
Předmět:
Zdroj: Xenotransplantation
Xenotransplantation, Wiley, 2019, pp.e12535. ⟨10.1111/xen.12535⟩
Xenotransplantation, 2019, pp.e12535. ⟨10.1111/xen.12535⟩
ISSN: 1399-3089
0908-665X
DOI: 10.1111/xen.12535⟩
Popis: International audience; Humans cannot synthesizeN-glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet-induced anti-Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet‐induced anti‐Neu5Gc Abs occurs in all normal individuals, endothelium activa-tion by elicited anti‐Neu5Gc Abs following a challenge with animal‐derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity‐purified anti‐Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc‐glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti-Neu5Gc Abs, compared with pre‐existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti‐Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre‐existing or anti‐human T‐cell globulin (ATG)‐elicited anti‐Neu5Gc Abs. Compared with pre‐existing anti‐Neu5Gc Abs, which are normal component of ECs environment, elicited anti‐Neu5Gc Abs down‐regulated 66 genes, including master genes of EC function. Furthermore, elicited anti-Neu5Gc Abs combined with complement‐containing serum down‐regulated most transcripts mobilized by serum alone. Both types of anti‐Neu5Gc Abs‐induced a dose‐ and com-plement‐dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre‐existing anti‐Neu5Gc Abs, ATG‐elicited anti‐Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro-inflammatory profile in vitro.
Databáze: OpenAIRE
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