LYMPHOCYTE HOMEOSTASIS AND AUTOIMMUNITY

Our team focuses on the mechanisms of  B- and T-cell tolerance breakdown leading to the development of autoimmunity during autoimmune diseases (in particular systemic lupus erythematosus (SLE), antiphospholipid syndrome, and systemic sclerosis) and during primary immunodeficiencies, using murine models (cell lines, transgenic mice) as well as human samples from patients. Our research is facilitated by our closed collaboration with the Clinical Immunology department of Strasbourg Hospital (Head: Pr Anne-Sophie Korganow) and with the French National reference center for systemic autoimmune diseases East South-West (RESO) (Head: Pr Thierry Martin).

Our team is composed of 6 permanent researchers (2 PU-PH-MD, 1 PU-PH-PharmD, 1 MCU-PH-MD, 1 MCU-PH-dentalD, and 1 MCU), 1 AHU, 2 engineers and students.

Current projects (Models):

  • Genetic studies and functional genomics for a better comprehension of B cell tolerance breakdown in autoimmune situations (SLE, antiphospholipid syndrome – Primary Immunodeficiencies)
  • Role of ZAP 70 in B cell tolerance (human/mouse)
  • PERSONALIS : Personalized medicine platform for autoimmune diseases
  • Consequences of STING gain of function on the development and phenotype of lymphocytes (CrisprCas9 mouse model)
  • Role of ERN1 in lymphocyte homeostasis and autoimmunity (CrisprCas9 mouse model)
  • Functional validation of a new phosphatase involved in T cell signaling (CrisprCas9 human cell lines, proteomic analysis)
  • Role of autophagy-related proteins in BCR trafficking (autophagy-deficient mouse models)
  • Role of lymphocytes’ autophagy in the development of systemic sclerosis in humans

COLLABORATIONS

Dr I. André (Imagine, France)

Dr F. Rieux-Laucat (Imagine, France)

Pr Y. Crow (Imagine, France)

Dr S. Chan & P. Kirstetter (IGMBC, France)

Pr H. Dollfus (U1112, France)

Dr V. Flacher (IBMC, France)

Dr N. Charlet (IGBMC, France)

Dr M. Rizzi (Freiburg, Germany)

Pr B. Grimbacher (Freiburg, Germany)

Dr M. Proietti (Freiburg, Germany)

Pr E. Meffre (Yale, USA)

Dr Markus Munschen (COH, USA)

Pr Enkelejda Miho (Basel, Switzerland)

Pr JL Casanova and S Dupuis-Boisson (NY, USA)

FUNDINGS

  • Agence Nationale de la Recherche (ANR)
  • Interreg & Offensive Sciences
  • Idex (University of Strasbourg)
  • Fondation pour la Recherche Médicale (FRM)
  • Arthritis Foundation
  • SATT Connectus
  • Centre de référence des déficits immunitaires héréditaires (CEREDIH)
  • Groupe Français de Recherche sur la sclérodermie (GFRS)
  • Association des sclérodermiques de France (ASF)
  • Groupement Interrégional de Recherche clinique et d’innovation de l’Est (GIRCI-Est).
  • CSL Behring
  • LFB

RECENT MAJOR PUBLICATIONS

Gies V., Guffroy A., Danion F., Billaud B., Keime C., Fauny J.-D., Susini S, Soley A., Martin T., Pasquali J.-L., Gros F., André-Schmutz I., Soulas-Sprauel P., Korganow A.-S. B cells differentiate in Human thymus and express AIRE. J Allergy Clin Immunol. 2017. 139(3):1049-1052.

Gies V., Wagner A, Seifert C., Guffroy A., Fauny J-D. Knapp A-M, Pasquali J-L., Martin T., Hélène Dumortier H., Korganow A-S., Soulas-Sprauel P. Identification of autoreactive B cells with labeled nucleosomes. Scientific reports. 2017 Apr 4;7(1):602.

Guffroy A., Mourot-Cottet R., Gérard L., Gies V., Lagresle C., Pouliet A., Nitschké P., Hanein S., Bienvenu B., Chanet V., Donadieu J., Gardembas M., Karmochkine M., Nove-Josserand R., Martin T., Poindron V., Soulas-Sprauel P., Rieux-Laucat F., Fieschi C., Oksenhendler E., André-Schmutz I., Korganow AS. DEFI study group. Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome. J Clin Immunol. 2017 Aug 26.

Sanges S., Rivière S., Mekinian A., Martin T., et al. Intravenous immunoglobulins in systemic sclerosis: data from a French nationwide cohort of 46 patients and review of the literature. Autoimmunity reviews. 2017; 16(4) : 377-384.

Gies V., Bouis D., Martin M., Pasquali J-L., Martin T., Korganow AS., Soulas-Sprauel P. Phenotyping of autoreactive B cells with labeled nucleosomes in 56R transgenic mice. Scientific reports. 2017 Oct 16;7(1):13232.

Gámez-Díaz L., Neumann J., Jäger F., Proietti M., Felber F.,Soulas-Sprauel P., Perruzza L., Grassi F., Kögl T., Aichele P., Kilimann M., Grimbacher B., Jung S. Immunological phenotype of the murine Lrba knockout. Immunol Cell Biol. 2017 Oct;95(9):789-802.

Pe. Gavand, I. Serio, L. Arnaud, N. Costedoat-Chalumeau, J. Carvelli, A.Dossier, O. Hinschberger, L. Mouthon, V. Le Guern, As. Korganow, V. Poindron, C.Gourguechon, C. Lavigne, F. Maurier , G. Labro , M. Heymonet, M. Artifoni, A. Brabant Viau, C. Deligny, T. Sene, L.Terriou, J. Sibilia, A. Mathian, C. Bloch-Queyrat, C. Larroche, Z. Amoura, T. Martin. Clinical Spectrum And Therapeutic Management Of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome: A Study Of 103 Episodes In 89 Adult Patients. Autoimmunity Reviews. 2017 ; 16(7) : 743-749.

Gies V., Schickel J-N., Jung S., Joublin A., Glauzy S., Knapp A-M., Soley A., Poindron V., Guffroy A., Choi J-H., Gottenberg J-E., Anolik J.H., Martin T., Soulas-Sprauel P., Meffre E., Korganow A-S.. Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus.. JCI Insight. 2018 Mar 8;3(5). pii: 96795.

Simoni L., Delgado V., Ruer-Laventie J., Bouis D., Soley A., Heyer V., Robert I., Gies V., Martin T., Korganow A-S., Reina San Martin B., Soulas-Sprauel P.Trib1 is overexpressed in systemic lupus erythematosus, while it regulates immunoglobulin production in murine B cells. Frontiers Immunol. 2018 Mar 15;9:373.

Murera D., Arbogast F., Arnold J., Bouis D., Muller S. and Gros F. CD4 T cell autophagy is integral to memory maintenance. Scientific Reports. 2018. 8(1): 5951.

Arbogast F. and Gros F. Lymphocyte autophagy in homeostasis, activation and inflammatory diseases. Frontiers in Immunology. 2018, 9:1801.

Jung S, Gámez-Díaz L, Proietti M, Grimbacher B. Immune TOR-opathies, a Novel Disease Entity in Clinical Immunology. Front Immunol. 2018 May 9;9:966. Review.

Bouis D., Kirstetter P., Arbogast F., Lamon D., Delgado V., Jung S., Ebel C., Jacobs H., Knapp A-M., Jeremiah N., Belot A., Martin T., Crow Y.J., André-Schmutz I., Korganow A-S., Rieux-Laucat F., Soulas-Sprauel P. Severe combined immunodeficiency in Sting V154M/WTmice. J Allergy Clin Immunol. 2019. 143(2):712-725.e5. doi: 10.1016/j.jaci.2018.04.034.

Dieudonné, Y., Gies, V., Guffroy, A., Keime, C., Bird, A.K., Liesveld, J., Barnas, J.L., Poindron, V., Douiri, N., Soulas-Sprauel, P., Martin, T., Meffre, E., Anolik, J.H., Korganow, A.-S. Transitional B cells in quiescent SLE: An early checkpoint imprinted by IFN. J. Autoimmunity. 2019. 102:150-158. doi: 10.1016/j.jaut.2019.05.002.

Herber M, Mertz P, Dieudonné Y , Guffroy B, Jung S, Gies V, Korganow AS, Guffroy A. Primary immunodeficiencies and lymphoma: a systematic review of literature. Leuk Lymphoma. 2019 Oct 3:1-11. doi: 10.1080/10428194.2019.1672056.

Arbogast F., Arnold J., Hammann P., Kuhn L., Chicher J., Murera D., Weishaar J., Muller S., Fauny J.D., Gros F. ATG5 is required for B cell polarization and presentation of particulate antigens. Autophagy. 2019, 15(2):280-294. doi: 10.1080/15548627.2018.1516327.

Dieudonné Y, Guffroy A, Vollmer O, Carapito R, Korganow AS. IKZF1 Loss-of-Function Variant Causes Autoimmunity and Severe Familial Antiphospholipid Syndrome. J Clin Immunol. 2019 May;39(4):353-357. doi: 10.1007/s10875-019-00643-2. Epub 2019 May 14.

Guffroy A, Dieudonné Y, Uring-Lambert B, Goetz J, Alembik Y, Korganow AS. Infection risk among adults with down syndrome: a two group series of 101 patients in a tertiary center. Orphanet J Rare Dis. 2019 Jan 11;14(1):15. doi: 10.1186/s13023-018-0989-x.

Guffroy A, Martin T, Korganow AS. Adolescents and young adults (AYAs) affected by chronic immunological disease: A tool-box for success during the transition to adult care. Clin Immunol. 2018 Dec;197:198-204. doi: 10.1016/j.clim.2018.10.010. Epub 2018 Oct 19.

Smith N, Rodero MP, Bekaddour N, Bondet V, Ruiz-Blanco YB, Harms M ,Mayer B , Badder-Meunier B, Quartier P, Bodemer C, Baudouin V, Dieudonné Y, Kirchhoff F, Sanchez Garcia E , Charbit B, Leboulanger N, Jahrsdörfer B, Richard Y, Korganow AS, Münch J, Nisole S, Duffy D, Herbeuval JP. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement-A new target for lupus treatment. Sci Adv. 2019 Jul 10;5(7):eaav9019. doi: 10.1126/sciadv.aav9019. eCollection 2019 Jul.