U1160 - Team 1 “Homeostatic and Pathological Chemokine-Regulated Interplays between Lymphocytes and their Microenvironment”

 

 Team leader : Karl Balabanian, DR2 Inserm, Team Leader

Deputy team leader : Marion Espéli, CRCN Inserm, Deputy Team Leader

 

Composition

BALABANIAN Karl (DR2 INSERM, HDR)

ESPÉLI Marion (CRCN INSERM, HDR)

ANGINOT Adrienne (CRCN INSERM, HDR in progress)

DULPHY Nicolas (MCU-PH Univ. Paris, APHP, HDR)

REA Delphine (PH APHP)

LERECLUS Emilie (IE INSERM)

BONAUD Amélie (Post-Doctorante)

LEMOS Julia (Post-Doctorante)

BISIO Valeria (Post-Doctorante)

RONDEAU Vincent (PhD student)

BOY Maxime (PhD student)

ZHAO Lin-Pierre (MD-PhD student)

ABOU NADER Zeina (PhD student)

KHAMYATH Mélanie (PhD student)

MOULIN Clémentine (Master 2 student)

SCHELL Bérénice (Master 2 student)

Main topic:

Our activities are centered on the interplays established between innate (NK, ILC) or adaptive (multipotent progenitors/MPP, plasma cells/PC) lymphoid cells and their microenvironment with a special focus on chemokine signaling in the bone marrow (BM). This is addressed at steady-state and under specific pathological conditions that arise in the BM: the WHIM Syndrome (WS), a rare immune-hematological disorder, Waldenström’s Macroglobulinemia (WM), a lymphoplasmacytic lymphoma with IgM monoclonal protein, and Myelodysplastic Syndromes (MDS) whom the evolution is dominated by the risk of progression into Acute Myeloid Leukemia (AML).

 

Scientific strategy:

 

The project is divided in three interconnected axes:

 

1) Cartography of BM localization and fate of MPP/PC and identification of the molecular interplays between MPP, PC and their BM niches in health and disease. Led by KB (MPP) and ME (PC).

2) Direct and stroma-mediated influence of MDS blasts on innate lymphopoiesis. Led by ND.

3) Dynamics of bone stroma and modelling of normal and pathologic HSPC and PC niches. Led by AA.

 

We are using a combination of classic immunological (e.g. Flow cytometry, confocal microscopy, in vitro functional assays) and cutting-edge (e.g Single-cell transcriptomics, artificial intelligence-driven image analysis, complex co-culture systems) technologies to address how lymphoid cells and their environment communicate in a bi-directional manner. We work on human samples and original genetically modified mouse models to dissect how this dialogue might be impaired in the course of immunodeficiencies and malignancies.

 

Our international, dynamic and enthusiastic team is always looking for new members eager to join the adventure.

 

 

Ten main outputs during the 2015-2020 period

 

1. BONAUD, A., Clare, S., BISIO, V., Sowerby, JM., Yao, S., Ostergaard, H., BALABANIAN, K., Smith, KGC., and ESPELI, M. (2020). Leupaxin Expression Is Dispensable for B Cell Immune Responses. Front Immunol 11, 466.

 

2. Boutin, L., Arnautou, P., Trignol, A., Ségot, A., Farge, T., Desterke, C., Soave, S., Clay, D., Raffoux, E., Sarry, JE., Malfuson, JV., Lataillade, JJ., Le Bousse-Kerdilès, MC., and ANGINOT, A. (2020). Mesenchymal stromal cells confer chemoresistance to myeloid leukemia blasts through Side Population functionality and ABC transporter activation. Haematologica 105, 987-9998.

 

3. ESPELI, M., Bashford-Rogers, R., Sowerby, JM., Alouche, N., Wong, L., Denton, AE., Linterman, MA., and Smith, KGC. (2019). FcγRIIb Differentially Regulates Pre-Immune and Germinal Center B Cell Tolerance in Mouse and Human. Nat Commun 10,1970.

 

4. Freitas, C., RONDEAU, V., and BALABANIAN, K. (2018). New method to obtain lymphoid progenitors. Patent WO/2018/177971 (PCT/EP2018/057580). PATENT

 

5. REA, D., Henry, G., Khaznadar, Z., Etienne, G., Guilhot, F., Nicolini, F., Guilhot, J., Rousselot, P., Huguet, F., Legros, L., Gardembas, M., Dubruille, V., Guerci-Bresler, A., Charbonnier, A., Maloisel, F., Ianotto, JC., Villemagne, B., Mahon, FX., Moins-Teisserenc, H., DULPHY, N., and Toubert, A. (2017). Natural killer cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study. Haematologica 102, 1368-1377.

6. Freitas, C., Wittner, M., Nguyen, J., RONDEAU, V., Biajoux, V., Aknin, M.L., Gaudin, F., Beaussant-Cohen, S., Bertrand, Y., Bellanne-Chantelot, C., Donadieu, J., Bachelerie, F., ESPELI, M., Dalloul, A., Louache, F.*, and BALABANIAN, K.* (2017). Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization. J Exp Med 214, 2023-2040.*Co-senior authors

 

7. REA, D., Nicolini, FE., Tulliez, M., Guilhot, F., Guilhot, J., Guerci-Bresler, A., Gardembas, M., Coiteux, V., Guillerm, G., Legros, L., Etienne, G., Pignon, JM., Villemagne, B., Escoffre-Barbe, M., Ianotto, JC., Charbonnier, A., Johnson-Ansah, H., Noel, MP., Rousselot, P., and Mahon, FX.; France Intergroupe des Leucémies Myéloïdes Chroniques. (2017). Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood 129, 846-854.

 

8. Biajoux, V., Natt, J., Freitas, C., Alouche, N., Sacquin, A., Hemon, P., Gaudin, F., Fazilleau, N., ESPELI, M.*, and BALABANIAN, K.* (2016). Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization. Cell Rep 17, 193-205.*Co-senior authors

 

9. Desnoyer, A., Dupin, N., Assoumou, L., Carlotti, A., Gaudin, F., Deback, C., Peytavin, G., Marcelin, A.G., Boue, F., BALABANIAN, K.*, and Pourcher, V.* ANRS 154 LENAKAP trial group (2016). Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions. Br J Dermatol 175, 1251-1262.*Co-senior authors

 

10. Bignon, A., Regent, A., Klipfel, L., Desnoyer, A., de la Grange, P., Martinez, V., Lortholary, O., Dalloul, A., Mouthon, L., and BALABANIAN, K. (2015). DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia. Blood 125, 2507-2518.

 

Major grants during the 2015-2020 period

JCJC ANR 2019 PC-SEC

Ligue contre le Cancer project grant 2019

IDEX-Université de Paris “Dynamique de Recherche” 2019

Association St-Louis pour la recherche sur les Leucémies 2018

ARC project grant 2018

Fondation Arthritis 2018

POC Inserm Transfert 2017

PRC ANR 2017 Osteovalymph

PRT-K INCa/DGOS 2017 BM-Immune-MDS

Association Force Hémato 2017

Association Laurette Fugain 2016

ANR@RAction 2015 AUTO-PLASMO

Labex LERMIT “Target” and Junior Team Leader 2015

 

Main networks

GDR 3697 MicroNiT

IHU THEMA

Institut Carnot OPALE

FHU Prothee

FHU TRUE

COST EuNet Innochron network

 

Alumni

V. Biajoux (2009-13)

A. Bignon (2010-14)

C. Freitas (2012-16)

A. Desnoyer (2012-15)

J. Nguyen (2014-2018)

N. Alouche (2014-2018)

J. Natt (2014-2017)

L. Klipfel (2012-15)