Scientific interest

The members of the Lymphopoiesis Unit have two main research interests:

 

Lymphocyte development

 

Hematopoietic stem cells (HSC) are generated during a short time-window in fetal life and colonize first the fetal liver, the major hematopoietic organ in the embryo and later the bone marrow that produces blood cells throughout life. While T and B cells are constantly generated, small subsets of lymphocytes are preferentially produced during fetal development (some types of gd T cells, of innate lymphoid cells and B1 B cells). The establishment of the immune system is a stepwise process that is initiated during fetal life and abnormal events during this period can lead to the development of leukemia or to immune dysfunctions, later in life. Immune deficiencies occur in a number of pathologic conditions leading to defective responses to antigenic challenges. Lymphopenia is frequently observed in patients subjected to allogeneic bone marrow transplantation. With ageing, lymphocyte production is severely decreased and although the number of peripheral lymphocytes is usually maintained, they are memory cells associated with benign clonal expansions. Any attempts to reestablishment a normal immune system requires an understanding of the developmental processes leading to its generation.

We study lymphocyte development in fetal liver and bone marrow with the aim to unravel the molecular mechanisms determining 1. commitment of multipotent progenitors into the different lymphocyte populations and 2. the preferential generation of lymphoid subsets in fetal or adult life.

 

The hematopoietic system and inflammation

 

The production of mature blood cells in the hematopoietic organs, mainly relies on the expansion of lineage-committed progenitors. HSCs undergo expansion in fetal liver to reach the size of the adult compartment in contrast, in the bone marrow, only a fraction is rapidly cycling while most HSC are resting (also designated as dormant HSC). Dormant HSC are rapidly and efficiently activated in response to stress signals, the most common of which is inflammation. Two basic mechanisms are involved in the response of HSC to bacterial and viral products. One, indirect, operates through cytokines, released by stromal and immune cells. Inflammatory cytokines can lead to the production of large numbers of myeloid cells with decreased lymphocyte production. A direct detection by hematopoietic progenitors of pathogen products, on the other hand, induces cell cycle and myeloid differentiation. Interestingly, repeated stimulation through pathogen associated molecular products leads to the exhaustion of the HSC compartment. Similar phenomenon has also been reported in HSC from aged individuals that progressively lose the capacity to reconstitute the lymphoid compartment, leading to deficits in the immune response. The effect of anti-inflammatory cytokines in hematopoiesis has not been analyzed and the role of the stromal compartment in this process is largely undocumented.

We are analyzing hematopoiesis 1. in a mouse model of overexpression of an anti-inflammatory cytokine, IL-10 2. the splenic stromal compartment in inflammatory conditions that lead to the development of an extra-medullary splenic hematopoiesis; 3. hematopoietic development and immune responses in a mouse model with an altered gradient of the chemokine CXCL12 in the extra-cellular compartment.

 

Updated on 11/03/2014

Contact

Lymphopoiesis Unit
Institut Pasteur
25 Rue du Docteur Roux
75724 Paris Cedex 15 FRANCE

     
Tel 33 1 45 68 82 55
Secretary 33 1 45 68 85 93
Fax 33 1 45 68 89 21

 

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