|Lymphocyte Development - Inserm U668|
|HEAD||CUMANO Ana / firstname.lastname@example.org|
|MEMBERS||Dr BANDEIRA Antonio / BOUCONTET Laurent / BURLEN-DEFRANOUX Odile / Dr CUMANO Ana / Dr GODIN Isabelle / Dr GOLUB Rachel / Dr KIEUSSEIAN Aurélie / LALANNE Ana Ines / LEMERCIER Brigitte / LIM Annick / PEREIRA DE SOUSA Ana Patricia / Dr PEREIRA Pablo / POSSOT Cécilie / RAMOND Cyrille / Dr VIEIRA Paulo / VOUGNY Marie-Christine
Hematopoietic cell development occurs through a succession of events involving hematopoietic stem cell generation, self-renewal, lineage commitment and differentiation. The different members of the Unit for Lymphocyte Development study in an integrative manner different aspects of hematopoietic and lymphocyte development. Hematopoietic Stem Cell generation. We have identified the site where hematopoietic stem cell generation occurs, in embryogenesis. We have been analyzing the properties of the newly generated hematopoietic stem cells, their capacity of engraftment and their requirements for further maturation and expansion in fetal liver that we consider being crucial aspects for the understanding of stem cell self-renewal and lineage determination.
Figure. Newly generated hematopoietic stem cells emerging from the ventral aspect of the aorta.
B-cell development. After migration to the hematopoietic organs, differentiation of hematopoietic stem cells occurs through the contact with the supporting stromal environment. Surface bound signaling molecules and cytokines determine lymphoid and myeloid lineage commitment and differentiation. We have shown that the fetal spleen environment has particular properties preventing hematopoietic stem cell renewal and favoring myeloid versus lymphoid commitment. We have been studying the requirements for B lymphocyte production during fetal and adult life. We showed that cytokines while promoting the expansion of hematopoietic precursors at consecutive stages of hematopoietic development could also have an instructive role in lineage commitment. In addition to cytokines other environmental factors can influence lymphocyte production. We are presently analyzing the cytokine-producing microenvironment in fetal liver and bone marrow and the role of Toll-like receptor signaling in B cell development.
T-cell development. In the thymus hematopoietic progenitors give rise to T lymphocytes that can be distinguished by surface marker expression and by function. We have established that allelic exclusion is obtained, in gd T cells, by different probabilities that a given δ chain has to pair with a γ chain. We are currently investigating the rules underlying lineage commitment of γδ versus αβ expressing T cells. In the thymus, another T cell subset of regulatory T cells is generated. We have shown that neonatal thymectomy, that results in a variable degree of autoimmune disease, does not lead to an absence of regulatory T cells and therefore that they are produced in the thymus before the third day of post-natal life. The physiology and the generation of these cells that regulate homeostasis and autoimmune disease are being studied.
Keywords: Hematopoiesis, cytokines, lymphopoiesis, regulatory T cells
Dias, S., Silva Jr, H., Cumano, A. & Vieira, P. 2005. Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. J. Exp. Med. 201 : 971-979
Bertrand J.Y., Desanti, G.E., Lo-Man, R., Leclerc, C., Cumano, A. & Golub, R. 2006. Fetal spleen stroma drives macrophage commitment. Development 133 : 3619-3628
Cumano, A. & Godin, I. 2007. Ontogeny of the hematopoietic system. Ann. Rev. Immunol. 25 : 745-785
Zuber, J., Viguier, M., Lemaitre, F., Senée, V., Patey, N., Elain, G., Geissmann, F., Fakhouri, F., Ferradini, L., Julier, C. & Bandeira, A. 2007. Severe Foxp3+ and naïve T lymphopenia in a non-IPEX form of autoimmune enteropathy combined with an immunodeficiency. Gastroenterology 132 : 1694-1704
Desanti, G.E., Cumano, A. & Golub, R. 2008. Identification of CD4int progenitors in mouse fetal spleen, a source of resident lymphoid cells. J. Leukocyte Biol, 83 : 1145-1154
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