Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

By C. Varol, Limor Landsman, D. Fogg, Liat Greenshtein, B. Gildor, R. Margalit, V. Kalchenko, F. Geissmann, Steffen Jung. Journal of Experimental Medicine, 2007

683 citations recorded by the source corpus.

The mononuclear phagocyte (MP) system is a body-wide macrophage (MΦ) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MΦ/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MΦs and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high “inflammatory” blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/1f41ccb5b9e36d21df8d3fa3422eb1acb60fb0eb

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In Immunology

1. Steffen Jung
2. A. Mildner
3. P. Italiani
4. D. Boraschi
5. Florent Ginhoux
6. F. Geissmann
7. Eric G. Pamer
8. C. Varol

Citations in the corpus

• Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen (2007, result): “This model is consistent with recent data suggesting a unique developmental pathway of splenic DCs compared with DCs in other organs (4, 41).”
• Monocyte-mediated defense against microbial pathogens. (2008, background): “Ly6C+ monocytes have a short transit time in the bloodstream and are not recovered from peripheral tissues in the absence of inflammation (16) but instead home to the bone marrow (20).”
• Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis (2012, neutral): “The differential appearance of the YFP label in Ly6C + and Ly6C − monocyte subsets indicated distinct temporal requirements for their creation, supporting the notion of their sequential generation (Sunderkotter et al., 2004; Varol et al., 2007,; Yrlid et al., 2006).”
• Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. (2012, methodology): “CD11c-DTR/WT BM chimeras were generated as reported (Varol et al., 2007).”
• Macrophages: development and tissue specialization. (2015, background): “Additionally, the monocyte origin of cells can be established through adoptive transfer experiments (49, 59).”
• Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responses (2007, background): “Mucosal APCs are derived from unique blood monocyte precursor”
• Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal (2013, background): “Chemokine receptor Ccr2 deficiency decreased by half the number of circulating Ly6C monocytes (Serbina and Pamer, 2006), which are proposed to represent a precursor for Ly6C monocytes (Varol et al., 2007).”
• Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas (2010, result): “Thus Mo-DCs are equivalent in many functional respects to DCs, except that they are monocyte dependent, whereas numerous prior studies show that classical DCs are monocyte independent (Naik et al., 2006; Varol et al., 2007) and derive from a committed pre-cDC in the bone marrow (Liu et al.”
• Monocyte recruitment during infection and inflammation (2011, background): “In the absence of inflammation, LY6C hi monocytes return to the bone marrow, where they are thought to differentiate into LY6C low monocyte”
• The origin and development of nonlymphoid tissue CD103+ DCs (2009, background): “These results are consistent with previous studies showing that monocytes fail to give rise to lung CD11c+CD11b cells (Landsman et al., 2007; Varol et al., 2007) but can produce lung CD11c+CD11b+ cells in the steady state.”