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Relationships between Distinct Blood Monocyte Subsets and Migrating Intestinal Lymph Dendritic Cells In Vivo under Steady-State Conditions

The Sir William Dunn School of Pathology, South Parks Road, Oxford, United Kingdom

The origins of dendritic cells (DCs) are poorly understood. In inflammation, DCs can arise from blood monocytes (M_Os), but their steady-state origin may differ, as shown for Langerhans cells. Two main subsets of M_Os, defined by expression of different chemokine receptors, CCR2 and CX₃CR1, have been described in mice and humans. Recent studies have identified the inflammatory function of CCR2^highCX₃CR1^low M_Os but have not defined unambiguously the origin and fate of CCR2^lowCX₃CR1^high cells. In this study, we show that rat M_Os can also be divided into CCR2^highCX₃CR1^low(CD43^low) and CCR2^lowCX₃CR1^high(CD43^high) subsets with distinct migratory properties in vivo. Using whole body perfusion to obtain M_Os, including the marginating pool, we show by adoptive transfer that CD43^low M_Os can differentiate into CD43^high M_Os in blood without cell division. By adoptive transfer of blood M_Os followed by collection of pseudoafferent lymph, we show for the first time that a small proportion of intestinal lymph DCs are derived from CCR2^lowCX₃CR1^high(CD43^high) blood M_Os in vivo under steady-state conditions. This study confirms one of the possible origins of CCR2^lowCX₃CR1^high blood M_Os and indicate that they may contribute to migratory intestinal DCs in vivo in the absence of inflammatory stimuli.

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