Origin of the Lamina Propria Dendritic Cell Network

Milena Bogunovic (1, 2) , Florent Ginhoux (2, 1) , Julie Helft (1, 2) , Limin Shang (2) , Daigo Hashimoto (1, 2) , Melanie Greter (1, 2) , Kang Liu (3) , Claudia Jakubzick (1, 2) , Molly A Ingersoll (1, 2) , Marylene Leboeuf (1, 2) , E Richard Stanley (4) , Michel C. Nussenzweig (3, 5) , Sergio A. Lira (2) , Gwendalyn Randolph (2, 1) , Miriam Merad (2, 1)

1 Department of Gene and Cell Medicine [New York]
2 PrIISM - Precision Immunology Institute [New-York]
3 Laboratory of Molecular Immunology [Rockfeller university, NY]
4 Department of Developmental and Molecular Biology [Albert Einstein CM, NY
5 HHMI - Howard Hughes Medical Institute [New York]

CX(3)CR1(+) and CD103(+) dendritic cells (DCs) in intestinal lamina propria play a key role in mucosal immunity. However, the origin and the developmental pathways that regulate their differentiation in the lamina propria remain unclear. We showed that monocytes gave rise exclusively to CD103(-)CX(3)CR1(+) lamina propria DCs under the control of macrophage-colony-stimulating factor receptor (M-CSFR) and Fms-like thyrosine kinase 3 (Flt3) ligands. In contrast, common DC progenitors (CDP) and pre-DCs, which give rise to lymphoid organ DCs but not to monocytes, differentiated exclusively into CD103(+)CX(3)CR1(-) lamina propria DCs under the control of Flt3 and granulocyte-macrophage-colony-stimulating factor receptor (GM-CSFR) ligands. CD103(+)CX(3)CR1(-) DCs but not CD103(-)CX(3)CR1(+) DCs in the lamina propria constitutively expressed CCR7 and were the first DCs to transport pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes. Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system.

Domaines: Immunologie

Milena Bogunovic, Florent Ginhoux, Julie Helft, Limin Shang, Daigo Hashimoto, et al.. Origin of the Lamina Propria Dendritic Cell Network. Immunity, 2009, 31 (3), pp.513-525. ⟨10.1016/j.immuni.2009.08.010⟩. ⟨pasteur-02439648⟩