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© Institut Pasteur
Macrophages et lymphocytes de souris. Image colorisée.
Project

The role of a gradient of the chemokine CXCL12 in hematopoietic development and in a normal immune response. (Collaboration with F. Arenzana-Seisdedos, granted ANR funding)

Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
09
Sep 2015
Status
Ongoing
Members
2
Structures
3

About

Interaction with heparan sulfate proteoglycans is supposed to provide chemokines with the capacity to immobilize on cell surface and extracellular matrix for accomplishing both tissue homing and signaling of attracted cells. The laboratory of F. Arenzana-Seisdedos, at Pasteur, engineered a mouse carrying a Cxcl12 gene (Cxcl12(Gagtm)) mutation that precludes interactions with heparan sulfate structures while not affecting CXCR4-dependent cell signaling of CXCL12 isoforms (α, β, γ). Cxcl12(Gagtm/Gagtm) mice develop normally, express normal levels of total and isoform-specific Cxcl12 mRNA, and show increased counting of circulating CD34+ hematopoietic precursor cells. We are analyzing the hematopoietic progenitor compartments in the BM and the lymphoid compartment in the secondary lymphoid organs of mutant mice. Our experiments aim at elucidating the role of CXCL12 gradients in hematopoietic development and in immune responses.

Fundings