AccueilAccueil>Research>Teams>Sébastien LACROIX-DESMAZES

Immunopathology and therapeutics immunointervention

The maintenance of immune homeostasis and effective immune response to pathogens implicate cross-talk between innate and adaptive immune cells. A dysregulation in immune homeostasis leads to the emergence of immunopathologies such as autoinflammatory conditions, or alloimmune responses to protein therapeutics.

In our first axis of research, we are exploring the role of circulating immunoglobulins, regulatory T cells (Treg) and B cells in the maintenance of immune homeostasis. The role of immunoglobulins in the immune tolerance is being explored through deciphering the cellular and molecular mechanisms of action of therapeutic intravenous immunoglobulin (IVIg). The study implicates both ex vivo models (through use of primary immune cells from healthy donors and from patients with autoimmune and inflammatory diseases) and in vivo models (such as experimental autoimmune encephalomyelitis). Besides, we are exploring the structural and biophysical bases of the induction of polyreactivity conferred to immunoglobulins by cofactors. We examine the consequences of the phenomenon under physiopathological conditions and the repercussion for therapy using IVIg and monoclonal antibodies.

 
Cleavage sites on factor VIII (FVIII)
for FVIII5hydrolyzing IgG from patients
with hemophilia A depicted on
the five5 domain model for FVIII
(cover page J  Immunol, 177(2) 2006).

Another aspect of our research is to decipher the immunogenicity of protein therapeutics (PT). Since the early 80’s, we have been implicated in research on the immunogenicity of factor VIII (FVIII). We pursue our work on FVIII as a model PT, and extend our studies to ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). This part of the project is multidisciplinary as it encompasses immunology, coagulation/hemostasis, and inflammation, with technical know-how in cell and molecular biology, in patients and in in vivo experimentation (in FVIII-deficient mice), biochemistry and biophysics. These studies have direct impact on patient management and delineation of novel less immunogenic protein therapeutics.

In parallel, we are investigating the cellular and molecular basis of immune response to Aspergillus fumigatus and Mycobacterium tuberculosis, and exploring the adjuvant potential of small molecule antagonists to CCR4 to transiently inhibit the suppressive effects of Tregs on antigen presenting cells.

Our research activities are supported by public and private funding from national and international agencies and are developed under the framework of International Associated Laboratory (INSERM, France-ICMR, India).

 

 Team Leader :  Sébastien LACROIX-DESMAZES (Dr)

Team Members : Jagadeesh BAYRY (Dr), Nina BOZINOVIC (Dr), Jordan DIMITROV (Dr), Srini V KAVERI (Dr)
Stéphanie AGUILEE (Tec), Victoria DAVENTURE (Eng), Sandrine DELIGNAT (Eng), Maxime LECERF (Eng), Justa LUENGO (Tech), Victorien ZHANG (Eng).
Mrinmoy DAS (PhD), Caroline GALEOTTI (PhD), Mathieu ING (PhD), Annaelle JAROSSAY (PhD), Anupama KARNAM (PhD), Naresh RAMBABU (PhD), Jules RUSSICK (PhD), Maud TEYSSANDIER (Post-Doc).

Administration : Veronique BARRAUD

Contact details: 33 1 44 27 81 93
Email: veronique.barraud@crc.jussieu.fr

Selected Publications

  • Gupta, N., S. Culina, Y. Meslier, J. Dimitrov, C. Arnoult, S. Delignat, B. Gangadharan, M. Lecerf, S. Justesen, V. Gouilleux-Gruart, B. L. Salomon, D. W. Scott, S. V. Kaveri, R. Mallone, and S. Lacroix-Desmazes. 2015. Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance. Sci Transl Med 7: 275ra221.
  • Lecerf M, Scheel T, Pashov AD, Jarossay A, Ohayon D, Planchais C, Mesnage S, Berek C, Kaveri SV, Lacroix-Desmazes S, Dimitrov JD. 2015. Prevalence and gene characteristics of antibodies with cofactor-induced HIV-1 specificity. J Biol Chem. 290:5203-5213.
  • Dimitrov, J. D., S. V. Kaveri, and S. Lacroix-Desmazes. 2014. Thermodynamic stability contributes to immunoglobulin specificity. Trends in biochemical sciences 39: 221-226.
  • Maddur MS, Sharma M, Hegde P, Stephen-Victor E, Pulendran B, Kaveri SV and Bayry J. 2014.  Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand. Nature Commun. 5: Article number 4092. doi: 10.1038/ncomms5092
  • Rayes, J., L. T. Roumenina, J. D. Dimitrov, Y. Repesse, M. Ing, O. Christophe, T. S. Jokiranta, L. Halbwachs-Mecarelli, A. Borel-Derlon, S. V. Kaveri, V. Fremeaux-Bacchi, and S. Lacroix-Desmazes. 2014. The interaction between factor H and VWF increases factor H cofactor activity and regulates VWF prothrombotic status. Blood 123: 121-125.
  • Trinath J, Hegde P, Sharma M, Maddur MS, Rabin M, Vallat JM, Magy L, Balaji KN, Kaveri SV and Bayry J. 2013. Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells. Blood 122:1419-1427.

View all publications

Link to PubMed

 

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