Minimal differentiation of classical monocytes as they survey steady state tissues and transport antigen to lymph nodes

By Claudia V. Jakubzick, E. Gautier, Sophie L Gibbings, Dorothy K. Sojka, A. Schlitzer, Theodore E Johnson, Stoyan Ivanov, Qiaonan Duan, S. Bala, T. Condon and 9 more. Immunity, 2013

748 citations recorded by the source corpus.

Summary It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C+ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes, but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHC II), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady state non-lymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/755670a8e03d71d20918ae59c155894466a9052b

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In Immunology

1. M. Guilliams
2. P. Italiani
3. D. Boraschi
4. A. Mildner
5. Steffen Jung
6. Florent Ginhoux
7. C. Varol
8. S. Yona

Citations in the corpus

• Macrophages: development and tissue specialization. (2015, background): “Finally, it was recently proposed that Ly6Chi monocytes persist in the steady state without commitment toward macrophage or DC-like fates and might contribute to antigen transport to lymph nodes (50) (Figure 3).”
• Inflammation, Immunity, and Hypertensive End-Organ Damage (2015, background): “recent evidence indicates that monocytes can traffic in and out of tissues without becoming macrophages.(14)”
• The fate and lifespan of human monocyte subsets in steady state and systemic inflammation (2017, background): “More recently, these cells have been shown to enter tissues under steady state and transport antigen to lymph nodes without differentiating (Jakubzick et al., 2013).”
• Skin Acute Wound Healing: A Comprehensive Review (2019, background): “In the steady state, monocyte emigration occurs constitutively, where they can remain within the tissue as monocytes, acquire antigenpresenting capabilities, or mature into macrophages [59, 60].”
• The role of macrophages in the resolution of inflammation. (2019, background): “In general, both tissue-resident and monocyte-derived macrophages demonstrate qualitatively similar changes in gene expression in response to injury, but these responses are more robust in monocyte-derived cells (9) and disproportionately affect physiologic measures of injury.”
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “In any case, we will bear in mind the notion that the tissue macrophages can maintain their number in the absence of monocyte precursors both in steady-state conditions (12, 48, 64, 86) as well as in genetically or experimentally monocytopenic situations (94, 95).”